Skip to main content
SpringerLink
Log in

Futuristic Methods for Determining HIV Co-receptor Use

  • Chapter
  • First Online:
Book cover Global Virology III: Virology in the 21st Century

Abstract

HIV infection of two key immune cells, CD4+ T cells and macrophages, plays a major role in the establishment of HIV infection and the seeding of the latent reservoir. There is a critical gap in our understanding of the determinants of viral tropism for these cell types and the molecular Env-receptor interactions involved. The development of novel futuristic methods including machine learning and neural network approaches, will allow the generation of sophisticated genotypic predication algorithms which will greatly enhance accurate HIV coreceptor usage identification within the clinic. Furthermore, advancements in surface plasmon resonance, biolayer interferometry and glycol-FRET technologies will be fundamental for real time investigation of molecular mechanisms involvement in Env-receptor interactions, which will enhance our understanding of coreceptor usage and viral tropism determinants. These technologies will be important for the development and improvement of therapeutic efficacy, novel entry inhibitors and assist vaccine design.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Finkel TH, Tudor-Williams G, Banda NK, Cotton MF, Curiel T, Monks C, et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med. 1995;1(2):129–34.

    Article  CAS  PubMed  Google Scholar 

  2. Phair J, Jacobson L, Detels R, Rinaldo C, Saah A, Schrager L, et al. Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 1992;5(5):490–6.

    Article  CAS  PubMed  Google Scholar 

  3. Munoz A, Wang MC, Bass S, Taylor JM, Kingsley LA, Chmiel JS, et al. Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. Multicenter AIDS Cohort Study Group. Am J Epidemiol. 1989;130(3):530–9.

    Article  CAS  PubMed  Google Scholar 

  4. Hendriks JC, Medley GF, van Griensven GJ, Coutinho RA, Heisterkamp SH, van Druten HA. The treatment-free incubation period of AIDS in a cohort of homosexual men. AIDS (London, England). 1993;7(2):231–9.

    Article  CAS  Google Scholar 

  5. Hendriks JC, Satten GA, van Ameijden EJ, van Druten HA, Coutinho RA, van Griensven GJ. The incubation period to AIDS in injecting drug users estimated from prevalent cohort data, accounting for death prior to an AIDS diagnosis. AIDS (London, England). 1998;12(12):1537–44.

    Article  CAS  Google Scholar 

  6. Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996;272(5265):1167–70.

    Article  CAS  PubMed  Google Scholar 

  7. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278(5341):1295–300.

    Article  CAS  PubMed  Google Scholar 

  8. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5(5):512–7.

    Article  CAS  PubMed  Google Scholar 

  9. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997;278(5341):1291–5.

    Article  CAS  PubMed  Google Scholar 

  10. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998;393(6686):648–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, Hendrickson WA, et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature. 1998;393(6686):705–11.

    Article  CAS  PubMed  Google Scholar 

  12. Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science. 1998;280(5371):1884–8.

    Article  CAS  PubMed  Google Scholar 

  13. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9(3):301–9.

    Article  CAS  PubMed  Google Scholar 

  14. Saphire AC, Bobardt MD, Zhang Z, David G, Gallay PA. Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages. J Virol. 2001;75(19):9187–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100(5):587–97.

    Article  CAS  PubMed  Google Scholar 

  16. Chen B, Vogan EM, Gong H, Skehel JJ, Wiley DC, Harrison SC. Structure of an unliganded simian immunodeficiency virus gp120 core. Nature. 2005;433(7028):834–41.

    Article  CAS  PubMed  Google Scholar 

  17. Huang CC, Tang M, Zhang MY, Majeed S, Montabana E, Stanfield RL, et al. Structure of a V3-containing HIV-1 gp120 core. Science. 2005;310(5750):1025–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cormier EG, Dragic T. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol. 2002;76(17):8953–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kwon YD, Finzi A, Wu X, Dogo-Isonagie C, Lee LK, Moore LR, et al. Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc Natl Acad Sci U S A. 2012;109(15):5663–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gallo SA, Finnegan CM, Viard M, Raviv Y, Dimitrov A, Rawat SS, et al. The HIV Env-mediated fusion reaction. Biochim Biophys Acta. 2003;1614(1):36–50.

    Article  CAS  PubMed  Google Scholar 

  21. Lyumkis D, Julien JP, de Val N, Cupo A, Potter CS, Klasse PJ, et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013;342(6165):1484–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gallo SA, Puri A, Blumenthal R. HIV-1 gp41 six-helix bundle formation occurs rapidly after the engagement of gp120 by CXCR4 in the HIV-1 Env-mediated fusion process. Biochemistry. 2001;40(41):12231–6.

    Article  CAS  PubMed  Google Scholar 

  23. Markosyan RM, Leung MY, Cohen FS. The six-helix bundle of human immunodeficiency virus Env controls pore formation and enlargement and is initiated at residues proximal to the hairpin turn. J Virol. 2009;83(19):10048–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tabler CO, Lucera MB, Haqqani AA, McDonald DJ, Migueles SA, Connors M, et al. CD4(+) memory stem cells are infected by HIV-1 in a manner regulated in part by SAMHD1 expression. J Virol. 2014;88(9):4976–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A. 1997;94(5):1925–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A. 1999;96(9):5215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cashin K, Paukovics G, Jakobsen MR, Ostergaard L, Churchill MJ, Gorry PR, et al. Differences in coreceptor specificity contribute to alternative tropism of HIV-1 subtype C for CD4(+) T-cell subsets, including stem cell memory T-cells. Retrovirology. 2014;11:97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Flynn JK, Paukovics G, Cashin K, Borm K, Ellett A, Roche M, et al. Quantifying susceptibility of CD4+ stem memory T-cells to infection by laboratory adapted and clinical HIV-1 strains. Viruses. 2014;6(2):709–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Jobe O, Trinh HV, Kim J, Alsalmi W, Tovanabutra S, Ehrenberg PK, et al. Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region. J Leukoc Biol. 2016;99(6):1089–106.

    Article  CAS  PubMed  Google Scholar 

  30. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996;381(6584):661–6.

    Article  CAS  PubMed  Google Scholar 

  31. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996;2(11):1240–3.

    Article  CAS  PubMed  Google Scholar 

  32. Yi Y, Isaacs SN, Williams DA, Frank I, Schols D, De Clercq E, et al. Role of CXCR4 in cell-cell fusion and infection of monocyte-derived macrophages by primary human immunodeficiency virus type 1 (HIV-1) strains: two distinct mechanisms of HIV-1 dual tropism. J Virol. 1999;73(9):7117–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Berger EA, Doms RW, Fenyo EM, Korber BT, Littman DR, Moore JP, et al. A new classification for HIV-1. Nature. 1998;391(6664):240.

    Article  CAS  PubMed  Google Scholar 

  34. Gorry PR, Bristol G, Zack JA, Ritola K, Swanstrom R, Birch CJ, et al. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity. J Virol. 2001;75(21):10073–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Musich T, O’Connell O, Gonzalez-Perez MP, Derdeyn CA, Peters PJ, Clapham PR. HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+ T-cells than envelopes highly adapted for macrophages. Retrovirology. 2015;12:25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Flynn JK, Paukovics G, Moore MS, Ellett A, Gray LR, Duncan R, et al. The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets. Virology. 2013;442(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  37. Gray L, Sterjovski J, Churchill M, Ellery P, Nasr N, Lewin SR, et al. Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome. Virology. 2005;337(2):384–98.

    Article  CAS  PubMed  Google Scholar 

  38. Gray L, Roche M, Churchill MJ, Sterjovski J, Ellett A, Poumbourios P, et al. Tissue-specific sequence alterations in the human immunodeficiency virus type 1 envelope favoring CCR5 usage contribute to persistence of dual-tropic virus in the brain. J Virol. 2009;83(11):5430–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Parker ZF, Iyer SS, Wilen CB, Parrish NF, Chikere KC, Lee FH, et al. Transmitted/founder and chronic HIV-1 envelope proteins are distinguished by differential utilization of CCR5. J Virol. 2013;87(5):2401–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105(21):7552–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Margolis L, Shattock R. Selective transmission of CCR5-utilizing HIV-1: the ‘gatekeeper’ problem resolved? Nat Rev Microbiol. 2006;4:312–7.

    Article  CAS  PubMed  Google Scholar 

  42. van’t Wout AB, Kootstra NA, Mulder-Kampinga GA, Albrecht van Lent N. Macrophage-tropic variants initiate Human Immunodeficiency Virus type 1 infection after sexual, parenteral and vertical transmission. J Clin Invest. 1994;94:2060–7.

    Article  Google Scholar 

  43. Shaw GM, Hunter E. HIV transmission. Cold Spring Harb Perspect Med. 2012;2(11):a006965.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382(6593):722–5.

    Article  CAS  PubMed  Google Scholar 

  45. Schacker T, Little S, Connick E, Gebhard K, Zhang Z, Krieger J, et al. Productive infection of T cells in lymphoid tissues during primary and early Human Immunodeficiency Virus infection. J Infect Dis. 2001;183(4):555–62.

    Article  CAS  PubMed  Google Scholar 

  46. Pope M, Betjes MGH, Romani N, Hirmand H, Cameron PU, Hoffman L, et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell. 1994;78:389–98.

    Article  CAS  PubMed  Google Scholar 

  47. Cameron PU, Freudenthal PS, Barker JM, Gezelter S, Inaba K, Steinman RM. Dendritic cells exposed to Human Immunodeficiency Virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science. 1992;257:383–7.

    Article  CAS  PubMed  Google Scholar 

  48. Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 infection. N Engl J Med. 2011;364:1943–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Huang W, Toma J, Stawiski E, Fransen S, Wrin T, Parkin N, et al. Characterization of human immunodeficiency virus type 1 populations containing CXCR4-using variants from recently infected individuals. AIDS Res Hum Retrovir. 2009;25(8):795–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ochsenbauer C, Edmonds TG, Ding H, Keele BF, Decker J, Salazar MG, et al. Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages. J Virol. 2012;86(5):2715–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wilen CB, Parrish NF, Pfaff JM, Decker JM, Henning EA, Haim H, et al. Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol. 2011;85(17):8514–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Jakobsen MR, Ellett A, Churchill MJ, Gorry PR. Viral tropism, fitness and pathogenicity of HIV-1 subtype C. Futur Virol. 2010;5(2):219–31.

    Article  Google Scholar 

  53. Koot M, Keet IP, Vos AH, de Goede RE, Roos MT, Coutinho RA, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993;118(9):681–8.

    Article  CAS  PubMed  Google Scholar 

  54. Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR. Change in coreceptor use correlates with disease progression in HIV-1--infected individuals. J Exp Med. 1997;185(4):621–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Klatzmann D, Barre-Sinoussi F, Nugeyre MT, Danquet C, Vilmer E, Griscelli C, et al. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984;225(4657):59–63.

    Article  CAS  PubMed  Google Scholar 

  56. Masur H, Ognibene FP, Yarchoan R, Shelhamer JH, Baird BF, Travis W, et al. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989;111(3):223–31.

    Article  CAS  PubMed  Google Scholar 

  57. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003;9(6):727–8.

    Article  CAS  PubMed  Google Scholar 

  58. Doitsh G, Galloway NLK, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2014;505(7484):509–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cummins NW, Badley AD. Mechanisms of HIV-associated lymphocyte apoptosis: 2010. Cell Death Dis. 2010;1:e99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Richard J, Prevost J, Baxter AE, von Bredow B, Ding S, Medjahed H, et al. Uninfected bystander cells impact the measurement of HIV-specific antibody-dependent cellular cytotoxicity responses. MBio. 2018;9(2):e00358–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Richard J, Veillette M, Ding S, Zoubchenok D, Alsahafi N, Coutu M, et al. Small CD4 mimetics prevent HIV-1 uninfected bystander CD4 + T cell killing mediated by antibody-dependent cell-mediated cytotoxicity. EBioMedicine. 2016;3:122–34.

    Article  PubMed  Google Scholar 

  62. Moore JP, McKeating JA, Weiss RA, Sattentau QJ. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science. 1990;250(4984):1139–42.

    Article  CAS  PubMed  Google Scholar 

  63. Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200(6):761–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, McNeil A, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77(21):11708–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fevrier M, Dorgham K, Rebollo A. CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis. Viruses. 2011;3(5):586–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cossarizza A, Ortolani C, Mussini C, Borghi V, Guaraldi G, Mongiardo N, et al. Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome. J Infect Dis. 1995;172(1):105–12.

    Article  CAS  PubMed  Google Scholar 

  67. Norris PJ, Pappalardo BL, Custer B, Spotts G, Hecht FM, Busch MP. Elevations in IL-10, TNF-alpha, and IFN-gamma from the earliest point of HIV Type 1 infection. AIDS Res Hum Retrovir. 2006;22(8):757–62.

    Article  CAS  PubMed  Google Scholar 

  68. Parrish NF, Wilen CB, Banks LB, Iyer SS, Pfaff JM, Salazar-Gonzalez JF, et al. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin alpha4beta7. PLoS Pathog. 2012;8(5):e1002686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jakobsen MR, Cashin K, Roche M, Sterjovski J, Ellett A, Borm K, et al. Longitudinal analysis of CCR5 and CXCR4 usage in a cohort of antiretroviral therapy-naive subjects with progressive HIV-1 subtype C infection. PLoS One. 2013;8(6):e65950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gray LR, Roche M, Flynn JK, Wesselingh SL, Gorry PR, Churchill MJ. Is the central nervous system a reservoir of HIV-1? Curr Opin HIV AIDS. 2014;9(6):552–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Chavez L, Calvanese V, Verdin E. HIV latency is established directly and early in both resting and activated primary CD4 T cells. PLoS Pathog. 2015;11(6):e1004955.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Shan L, Deng K, Gao H, Xing S, Capoferri AA, Durand CM, et al. Transcriptional reprogramming during effector-to-memory transition renders CD4(+) T cells permissive for latent HIV-1 infection. Immunity. 2017;47(4):766–75.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15(8):893–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Soriano-Sarabia N, Bateson RE, Dahl NP, Crooks AM, Kuruc JD, Margolis DM, et al. Quantitation of replication-competent HIV-1 in populations of resting CD4+ T cells. J Virol. 2014;88(24):14070–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014;20(2):139–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jaafoura S, de Goer de Herve MG, Hernandez-Vargas EA, Hendel-Chavez H, Abdoh M, Mateo MC, et al. Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4(+) memory T Cells. Nat Commun. 2014;5:5407.

    Article  CAS  PubMed  Google Scholar 

  78. Klatt NR, Bosinger SE, Peck M, Richert-Spuhler LE, Heigele A, Gile JP, et al. Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals. PLoS Pathog. 2014;10(8):e1004345.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Hoeffel G, Ginhoux F. Fetal monocytes and the origins of tissue-resident macrophages. Cell Immunol. 2018;330:5–15.

    Article  CAS  PubMed  Google Scholar 

  80. Epelman S, Lavine Kory J, Randolph GJ. Origin and functions of tissue macrophages. Immunity. 2014;41(1):21–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Mass E. Delineating the origins, developmental programs and homeostatic functions of tissue-resident macrophages. Int Immunol. 2018;30(11):493–501.

    CAS  PubMed  Google Scholar 

  82. Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016;44(3):439–49.

    Article  CAS  PubMed  Google Scholar 

  83. Munro DAD, Hughes J. The origins and functions of tissue-resident macrophages in kidney development. Front Physiol. 2017;8:837.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rojas J, Salazar J, Martinez MS, Palmar J, Bautista J, Chavez-Castillo M, et al. Macrophage heterogeneity and plasticity: impact of macrophage biomarkers on atherosclerosis. Scientifica. 2015;2015:851252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Gordon S, Martinez-Pomares L. Physiological roles of macrophages. Pflugers Arch Eur J Physiol. 2017;469(3–4):365–74.

    Article  CAS  Google Scholar 

  87. Grainger JR, Konkel JE, Zangerle-Murray T, Shaw TN. Macrophages in gastrointestinal homeostasis and inflammation. Arch Eur J Physiol. 2017;469(3):527–39.

    Article  CAS  Google Scholar 

  88. Bain CC, Mowat AM. Macrophages in intestinal homeostasis and inflammation. Immunol Rev. 2014;260(1):102–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Koppensteiner H, Brack-Werner R, Schindler M. Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology. 2012;9:82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, et al. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature. 2011;474(7353):654–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Flynn JK, Gorry PR. In: Shapshak PSJ, Somboonwit C, Kuhn JH, editors. Role of macrophages in the immunopathogenesis of HIV-1 infection. New York: Springer; 2015.

    Chapter  Google Scholar 

  92. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014;6:13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Clayton KL, Garcia JV, Clements JE, Walker BD. HIV infection of macrophages: implications for pathogenesis and cure. Pathog Immun. 2017;2(2):179–92.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Porcheray F, Samah B, Leone C, Dereuddre-Bosquet N, Gras G. Macrophage activation and human immunodeficiency virus infection: HIV replication directs macrophages towards a pro-inflammatory phenotype while previous activation modulates macrophage susceptibility to infection and viral production. Virology. 2006;349(1):112–20.

    Article  CAS  PubMed  Google Scholar 

  95. Herbein G, Varin A. The macrophage in HIV-1 infection: from activation to deactivation? Retrovirology. 2010;7:33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Paiardini M, Muller-Trutwin M. HIV-associated chronic immune activation. Immunol Rev. 2013;254(1):78–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Aquaro S, Bagnarelli P, Guenci T, De Luca A, Clementi M, Balestra E, et al. Long-term survival and virus production in human primary macrophages infected by human immunodeficiency virus. J Med Virol. 2002;68(4):479–88.

    Article  PubMed  Google Scholar 

  98. Cassol E, Rossouw T, Malfeld S, Mahasha P, Slavik T, Seebregts C, et al. CD14(+) macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide. BMC Infect Dis. 2015;15:430.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Clayton KL, Collins DR, Lengieza J, Ghebremichael M, Dotiwala F, Lieberman J, et al. Resistance of HIV-infected macrophages to CD8(+) T lymphocyte-mediated killing drives activation of the immune system. Nat Immunol. 2018;19(5):475–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Crowe SM, Westhorpe CL, Mukhamedova N, Jaworowski A, Sviridov D, Bukrinsky M. The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol. 2010;87(4):589–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, et al. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12(4):234–48.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Tuttle DL, Harrison JK, Anders C, Sleasman JW, Goodenow MM. Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1. J Virol. 1998;72(6):4962–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Lewin SR, Sonza S, Irving LB, McDonald CF, Mills J, Crowe SM. Surface CD4 is critical to in vitro HIV infection of human alveolar macrophages. AIDS Res Hum Retrovir. 1996;12(10):877–83.

    Article  CAS  PubMed  Google Scholar 

  104. Flynn JK, Gorry PR. Stem memory T cells (TSCM)-their role in cancer and HIV immunotherapies. Clin Transl Immunol. 2014;3(7):e20.

    Article  CAS  Google Scholar 

  105. Gorry PR, Francella N, Lewin SR, Collman RG. HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies. J Leukoc Biol. 2014;95(1):71–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Peters PJ, Bhattacharya J, Hibbitts S, Dittmar MT, Simmons G, Bell J, et al. Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages. J Virol. 2004;78(13):6915–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Peters PJ, Sullivan WM, Duenas-Decamp MJ, Bhattacharya J, Ankghuambom C, Brown R, et al. Non-macrophage-tropic human immunodeficiency virus type 1 R5 envelopes predominate in blood, lymph nodes, and semen: implications for transmission and pathogenesis. J Virol. 2006;80(13):6324–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gorry PR, Taylor J, Holm GH, Mehle A, Morgan T, Cayabyab M, et al. Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate. J Virol. 2002;76(12):6277–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, et al. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A. 2006;103(41):15160–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11(11):723–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5(12):953–64.

    Article  CAS  PubMed  Google Scholar 

  112. Jambo KC, Banda DH, Kankwatira AM, Sukumar N, Allain TJ, Heyderman RS, et al. Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function. Mucosal Immunol. 2014;7(5):1116–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Mitsi E, Kamng’ona R, Rylance J, Solorzano C, Jesus Reine J, Mwandumba HC, et al. Human alveolar macrophages predominately express combined classical M1 and M2 surface markers in steady state. Respir Res. 2018;19(1):66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Burdo TH, Lackner A, Williams KC. Monocyte/macrophages and their role in HIV neuropathogenesis. Immunol Rev. 2013;254(1):102–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Joseph SB, Arrildt KT, Sturdevant CB, Swanstrom R. HIV-1 target cells in the CNS. J Neurovirol. 2015;21(3):276–89.

    Article  CAS  PubMed  Google Scholar 

  116. He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, et al. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature. 1997;385(6617):645–9.

    Article  CAS  PubMed  Google Scholar 

  117. Lavi E, Strizki JM, Ulrich AM, Zhang W, Fu L, Wang Q, et al. CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons. Am J Pathol. 1997;151(4):1035–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med. 2001;193(8):905–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bell JE. The neuropathology of adult HIV infection. Rev Neurol (Paris). 1998;154(12):816–29.

    CAS  Google Scholar 

  120. Best BM, Letendre SL, Koopmans P, Rossi SS, Clifford DB, Collier AC, et al. Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, tenofovir. J Acquir Immune Defic Syndr. 2012;59(4):376–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Kumar A, Abbas W, Herbein G. HIV-1 latency in monocytes/macrophages. Viruses. 2014;6(4):1837–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Chun TW, Fauci AS. Latent reservoirs of HIV: obstacles to the eradication of virus. Proc Natl Acad Sci U S A. 1999;96(20):10958–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Gras G, Kaul M. Molecular mechanisms of neuroinvasion by monocytes-macrophages in HIV-1 infection. Retrovirology. 2010;7:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Nath A, Clements JE. Eradication of HIV from the brain: reasons for pause. AIDS. 2011;25(5):577–80.

    Article  PubMed  Google Scholar 

  125. Alexaki A, Liu Y, Wigdahl B. Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res. 2008;6(5):388–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Igarashi T, Brown CR, Endo Y, Buckler-White A, Plishka R, Bischofberger N, et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): implications for HIV-1 infections of humans. Proc Natl Acad Sci U S A. 2001;98(2):658–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Brown D, Mattapallil JJ. Gastrointestinal tract and the mucosal macrophage reservoir in HIV infection. Clin Vaccine Immunol. 2014;21(11):1469–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Costiniuk CT, Jenabian MA. The lungs as anatomical reservoirs of HIV infection. Rev Med Virol. 2014;24(1):35–54.

    Article  PubMed  Google Scholar 

  129. King DF, Siddiqui AA, Buffa V, Fischetti L, Gao Y, Stieh D, et al. Mucosal tissue tropism and dissemination of HIV-1 subtype B acute envelope-expressing chimeric virus. J Virol. 2013;87(2):890–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. McElrath MJ, Smythe K, Randolph-Habecker J, Melton KR, Goodpaster TA, Hughes SM, et al. Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus. J Acquir Immune Defic Syndr. 2013;63(3):263–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Li L, Meng G, Graham MF, Shaw GM, Smith PD. Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5. Gastroenterology. 1999;116(5):1043–53.

    Article  CAS  PubMed  Google Scholar 

  132. Shen R, Meng G, Ochsenbauer C, Clapham PR, Grams J, Novak L, et al. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-kappaB activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Pathog. 2011;7(5):e1002060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Sharova N, Swingler C, Sharkey M, Stevenson M. Macrophages archive HIV-1 virions for dissemination in trans. EMBO J. 2005;24(13):2481–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Chu H, Wang JJ, Qi M, Yoon JJ, Wen X, Chen X, et al. The intracellular virus-containing compartments in primary human macrophages are largely inaccessible to antibodies and small molecules. PLoS One. 2012;7(5):e35297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood. 2008;111(9):4660–3.

    Article  CAS  PubMed  Google Scholar 

  136. Waki K, Freed EO. Macrophages and cell-cell spread of HIV-1. Viruses. 2010;2(8):1603–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Gousset K, Ablan SD, Coren LV, Ono A, Soheilian F, Nagashima K, et al. Real-time visualization of HIV-1 GAG trafficking in infected macrophages. PLoS Pathog. 2008;4(3):e1000015.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Hammonds JE, Beeman N, Ding L, Takushi S, Francis AC, Wang JJ, et al. Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1. PLoS Pathog. 2017;13(1):e1006181.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Castellano P, Prevedel L, Eugenin EA. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci Rep. 2017;7(1):12866.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Cribbs SK, Lennox J, Caliendo AM, Brown LA, Guidot DM. Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res Hum Retrovir. 2015;31(1):64–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984;312(5996):763–7.

    Article  CAS  PubMed  Google Scholar 

  142. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272(5263):872–7.

    Article  CAS  PubMed  Google Scholar 

  143. Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother. 2005;49(11):4721–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Lalezari JP, Henry K, O’Hearn M, Montaner JS, Piliero PJ, Trottier B, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175–85.

    Article  CAS  PubMed  Google Scholar 

  145. Roche M, Borm K, Flynn JK, Lewin SR, Churchill MJ, Gorry PR. Molecular gymnastics: mechanisms of HIV-1 resistance to CCR5 antagonists and impact on virus phenotypes. Curr Top Med Chem. 2016;16(10):1091–106.

    Article  CAS  PubMed  Google Scholar 

  146. Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359(14):1429–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Fatkenheuer G, Nelson M, Lazzarin A, Konourina I, Hoepelman AI, Lampiris H, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med. 2008;359(14):1442–55.

    Article  PubMed  Google Scholar 

  148. Cooper DA, Heera J, Ive P, Botes M, Dejesus E, Burnside R, et al. Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings. AIDS (London, England). 2014;28(5):717–25.

    Article  CAS  Google Scholar 

  149. Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010;201(6):803–13.

    Article  CAS  PubMed  Google Scholar 

  150. Roche M, Jakobsen MR, Sterjovski J, Ellett A, Posta F, Lee B, et al. HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism. J Virol. 2011;85(9):4330–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Roche M, Salimi H, Duncan R, Wilkinson BL, Chikere K, Moore MS, et al. A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirology. 2013;10:43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Tilton JC, Wilen CB, Didigu CA, Sinha R, Harrison JE, Agrawal-Gamse C, et al. A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. J Virol. 2010;84(20):10863–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, et al. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol. 2007;81(5):2359–71.

    Article  CAS  PubMed  Google Scholar 

  154. Flynn JK, Ellenberg P, Duncan R, Ellett A, Zhou J, Sterjovski J, et al. Analysis of clinical HIV-1 strains with resistance to maraviroc reveals strain-specific resistance mutations, variable degrees of resistance, and minimal cross-resistance to other CCR5 antagonists. AIDS Res Hum Retrovir. 2017;33(12):1220–35.

    Article  CAS  PubMed  Google Scholar 

  155. Reeves J, Coakley E, Petropoulos C, Whitcomb J. An enhanced sensitivity Trofile HIV coreceptor tropism assay for selecting patients for therapy with entry inhibitors targeting CCR5: a review of analytical and clinical studies. J Viral Entry. 2009;3(3):94–102.

    Google Scholar 

  156. Trinh L, Han D, Huang W, Wrin T, Larson J, Kiss L, et al. Validation of an enhanced sensitivity Trofile™ HIV-1 co-receptor tropism assay for selecting patients for therapy with entry inhibitors targeting CCR5. J Int AIDS Soc. 2008;11(1):P197.

    Article  Google Scholar 

  157. Su Z, Gulick RM, Krambrink A, Coakley E, Hughes MD, Han D, et al. Response to vicriviroc in treatment-experienced subjects using an enhanced sensitivity co-receptor tropism assay: reanalysis of AIDS Clinical Trials Group A5211. J Infect Dis. 2009;200(11):1724–8.

    Article  CAS  PubMed  Google Scholar 

  158. Toma J, Frantzell A, Hoh R, Martin J, Deeks S, Petropoulos C, et al., editors. Determining HIV-1 co-receptor tropism using PBMC proviral DNA derived from aviremic blood samples. The 17th conference on retroviruses and opportunistic infections (CROI) San Francisco; 2010.

    Google Scholar 

  159. Fouchier RA, Groenink M, Kootstra NA, Tersmette M, Huisman HG, Miedema F, et al. Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992;66(5):3183–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. De Jong JJ, De Ronde A, Keulen W, Tersmette M, Goudsmit J. Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol. 1992;66(11):6777–80.

    PubMed  PubMed Central  Google Scholar 

  161. Lengauer T, Sander O, Sierra S, Thielen A, Kaiser R. Bioinformatics prediction of HIV coreceptor usage. Nat Biotechnol. 2007;25(12):1407–10.

    Article  CAS  PubMed  Google Scholar 

  162. Hwang SS, Boyle TJ, Lyerly HK, Cullen BR. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991;253(5015):71–4.

    Article  CAS  PubMed  Google Scholar 

  163. Raymond S, Delobel P, Mavigner M, Ferradini L, Cazabat M, Souyris C, et al. Prediction of HIV type 1 subtype C tropism by genotypic algorithms built from subtype B viruses. J Acquir Immune Defic Syndr. 2010;53(2):167–75.

    Article  PubMed  Google Scholar 

  164. Sanchez V, Masia M, Robledano C, Padilla S, Ramos JM, Gutierrez F. Performance of genotypic algorithms for predicting HIV-1 tropism measured against the enhanced-sensitivity Trofile coreceptor tropism assay. J Clin Microbiol. 2010;48(11):4135–9.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Garrido C, Roulet V, Chueca N, Poveda E, Aguilera A, Skrabal K, et al. Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes. J Clin Microbiol. 2008;46(3):887–91.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Cashin K, Gray LR, Jakobsen MR, Sterjovski J, Churchill MJ, Gorry PR. CoRSeqV3-C: a novel HIV-1 subtype C specific V3 sequence based coreceptor usage prediction algorithm. Retrovirology. 2013;10:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Raymond S, Delobel P, Rogez S, Encinas S, Bruel P, Pasquier C, et al. Genotypic prediction of HIV-1 CRF01-AE tropism. J Clin Microbiol. 2013;51(2):564–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Jensen MA, Li FS, van ‘t Wout AB, Nickle DC, Shriner D, He HX, et al. Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol. 2003;77(24):13376–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Soulie C, Derache A, Aime C, Marcelin AG, Carcelain G, Simon A, et al. Comparison of two genotypic algorithms to determine HIV-1 tropism. HIV Med. 2008;9(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  170. Jensen MA, Coetzer M, van ‘t Wout AB, Morris L, Mullins JI. A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope V3 sequences. J Virol. 2006;80(10):4698–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Low AJ, Dong W, Chan D, Sing T, Swanstrom R, Jensen M, et al. Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AIDS (London, England). 2007;21(14):F17–24.

    Article  Google Scholar 

  172. Trabaud MA, Icard V, Scholtes C, Perpoint T, Koffi J, Cotte L, et al. Discordance in HIV-1 co-receptor use prediction by different genotypic algorithms and phenotype assay: intermediate profile in relation to concordant predictions. J Med Virol. 2012;84(3):402–13.

    Article  PubMed  Google Scholar 

  173. Kalu AW, Telele NF, Gebreselasie S, Fekade D, Abdurahman S, Marrone G, et al. Prediction of coreceptor usage by five bioinformatics tools in a large Ethiopian HIV-1 subtype C cohort. PLoS One. 2017;12(8):e0182384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Delgado E, Fernandez-Garcia A, Vega Y, Cuevas T, Pinilla M, Garcia V, et al. Evaluation of genotypic tropism prediction tests compared with in vitro co-receptor usage in HIV-1 primary isolates of diverse subtypes. J Antimicrob Chemother. 2012;67(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  175. Recordon-Pinson P, Soulie C, Flandre P, Descamps D, Lazrek M, Charpentier C, et al. Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study. Antimicrob Agents Chemother. 2010;54(8):3335–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Seclen E, Garrido C, Gonzalez Mdel M, Gonzalez-Lahoz J, de Mendoza C, Soriano V, et al. High sensitivity of specific genotypic tools for detection of X4 variants in antiretroviral-experienced patients suitable to be treated with CCR5 antagonists. J Antimicrob Chemother. 2010;65(7):1486–92.

    Article  CAS  PubMed  Google Scholar 

  177. Cashin K, Gray LR, Harvey KL, Perez-Bercoff D, Lee GQ, Sterjovski J, et al. Reliable genotypic tropism tests for the major HIV-1 subtypes. Sci Rep. 2015;5:8543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Kieslich CA, Tamamis P, Guzman YA, Onel M, Floudas CA. Highly accurate structure-based prediction of HIV-1 coreceptor usage suggests intermolecular interactions driving tropism. PLoS One. 2016;11(2):e0148974.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Poveda E, Briz V, Roulet V, Del Mar Gonzalez M, Faudon JL, Skrabal K, et al. Correlation between a phenotypic assay and three bioinformatic tools for determining HIV co-receptor use. AIDS (London, England). 2007;21(11):1487–90.

    Article  Google Scholar 

  180. Skrabal K, Low AJ, Dong W, Sing T, Cheung PK, Mammano F, et al. Determining human immunodeficiency virus coreceptor use in a clinical setting: degree of correlation between two phenotypic assays and a bioinformatic model. J Clin Microbiol. 2007;45(2):279–84.

    Article  CAS  PubMed  Google Scholar 

  181. Hoffman NG, Seillier-Moiseiwitsch F, Ahn J, Walker JM, Swanstrom R. Variability in the human immunodeficiency virus type 1 gp120 Env protein linked to phenotype-associated changes in the V3 loop. J Virol. 2002;76(8):3852–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Dimonte S, Babakir-Mina M, Mercurio F, Di Pinto D, Ceccherini-Silberstein F, Svicher V, et al. Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120(V3) signatures in the regulation of co-receptor usage. Virus Res. 2012;168(1–2):73–83.

    Article  CAS  PubMed  Google Scholar 

  183. Dimonte S, Mercurio F, Svicher V, D’Arrigo R, Perno CF, Ceccherini-Silberstein F. Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Retrovirology. 2011;8:33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Boyd MT, Simpson GR, Cann AJ, Johnson MA, Weiss RA. A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. J Virol. 1993;67(6):3649–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Thielen A, Lengauer T, Swenson LC, Dong WW, McGovern RA, Lewis M, et al. Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially. Antivir Ther. 2011;16(3):319–28.

    Article  CAS  PubMed  Google Scholar 

  186. Huang W, Toma J, Fransen S, Stawiski E, Reeves JD, Whitcomb JM, et al. Coreceptor tropism can be influenced by amino acid substitutions in the gp41 transmembrane subunit of human immunodeficiency virus type 1 envelope protein. J Virol. 2008;82(11):5584–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Huang W, Eshleman SH, Toma J, Fransen S, Stawiski E, Paxinos EE, et al. Coreceptor tropism in human immunodeficiency virus type 1 subtype D: high prevalence of CXCR4 tropism and heterogeneous composition of viral populations. J Virol. 2007;81(15):7885–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Coetzer M, Nedellec R, Cilliers T, Meyers T, Morris L, Mosier DE. Extreme genetic divergence is required for coreceptor switching in HIV-1 subtype C. J Acquir Immune Defic Syndr. 2011;56(1):9–15.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Diez-Fuertes F, Delgado E, Vega Y, Fernandez-Garcia A, Cuevas MT, Pinilla M, et al. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother. 2013;68(7):1471–85.

    Article  CAS  PubMed  Google Scholar 

  190. Schrider DR, Kern AD. Supervised machine learning for population genetics: a new paradigm. Trends Genet. 2018;34(4):301–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Tarca AL, Carey VJ, Chen XW, Romero R, Draghici S. Machine learning and its applications to biology. PLoS Comput Biol. 2007;3(6):e116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Saeys Y, Inza I, Larranaga P. A review of feature selection techniques in bioinformatics. Bioinformatics (Oxford, England). 2007;23(19):2507–17.

    Article  CAS  Google Scholar 

  193. Libbrecht MW, Noble WS. Machine learning applications in genetics and genomics. Nat Rev Genet. 2015;16(6):321–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Kumari S, Chouhan U, Suryawanshi SK. Machine learning approaches to study HIV/AIDS infection: a review. Biosci Biotechnol Res. 2017;10(1):34–43.

    Article  Google Scholar 

  195. Camacho DM, Collins KM, Powers RK, Costello JC, Collins JJ. Next-generation machine learning for biological networks. Cell. 2018;173(7):1581–92.

    Article  CAS  PubMed  Google Scholar 

  196. Yip KY, Cheng C, Gerstein M. Machine learning and genome annotation: a match meant to be? Genome Biol. 2013;14(5):205.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Ho TK, editor. Random decision forests. Document analysis and recognition, 1995, proceedings of the third international conference on; 1995: IEEE.

    Google Scholar 

  198. Torkkola K. Feature extraction by non parametric mutual information maximization. J Mach Learn Res. 2003;3:1415–38.

    Google Scholar 

  199. Boritz EA, Darko S, Swaszek L, Wolf G, Wells D, Wu X, et al. Multiple origins of virus persistence during natural control of HIV infection. Cell. 2016;166(4):1004–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Thielen A, Sichtig N, Kaiser R, Lam J, Harrigan PR, Lengauer T. Improved prediction of HIV-1 coreceptor usage with sequence information from the second hypervariable loop of gp120. J Infect Dis. 2010;202(9):1435–43.

    Article  CAS  PubMed  Google Scholar 

  201. Boisvert S, Marchand M, Laviolette F, Corbeil J. HIV-1 coreceptor usage prediction without multiple alignments: an application of string kernels. Retrovirology. 2008;5(1):110.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Pillai S, Good B, Richman D, Corbeil J. A new perspective on V3 phenotype prediction. AIDS Res Hum Retrovir. 2003;19(2):145–9.

    Article  CAS  PubMed  Google Scholar 

  203. Kumar R, Raghava GP. Hybrid approach for predicting coreceptor used by HIV-1 from its V3 loop amino acid sequence. PLoS One. 2013;8(4):e61437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Bzdok D, Krzywinski M, Altman N. Machine learning: supervised methods. Nat Methods. 2018;15:5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Dybowski JN, Heider D, Hoffmann D. Prediction of co-receptor usage of HIV-1 from genotype. PLoS Comput Biol. 2010;6(4):e1000743.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Bozek K, Lengauer T, Sierra S, Kaiser R, Domingues FS. Analysis of physicochemical and structural properties determining HIV-1 coreceptor usage. PLoS Comput Biol. 2013;9(3):e1002977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Xu S, Huang X, Xu H, Zhang C. Improved prediction of coreceptor usage and phenotype of HIV-1 based on combined features of V3 loop sequence using random forest. J Microbiol. 2007;45(5):441–6.

    CAS  PubMed  Google Scholar 

  208. McCulloch WS, Pitts W. A logical calculus of the ideas immanent in nervous activity. Bull Math Biophys. 1943;5(4):115–33.

    Article  Google Scholar 

  209. Werbos PJ. Beyond regression: new tools for prediction and analysis in the behavioral science. Thesis (Ph. D.). Appl. Math. Harvard University, January 1974.

    Google Scholar 

  210. Angermueller C, Parnamaa T, Parts L, Stegle O. Deep learning for computational biology. Mol Syst Biol. 2016;12(7):878.

    Article  PubMed  PubMed Central  Google Scholar 

  211. Krizhevsky A, Suskever I, Hinton GE. ImageNet classification with deep convolutional neural networks. Published in Advances in Neural Information Processing Systems 25 edited by F. Pereira and C.J.C. Burges and L. Bottou and K.Q. Weinberger. 2012. https://papers.nips.cc/paper/4824-imagenet-classification-with-deep-convolutional-neural-networks

  212. Graves A, Mohamed A-R, Hinton GE. Speech recognition with deep recurrent neural networks. Published in IEEE International Conference on Acoustics, Speech and Signal Processing, 26–31th May 2013, Vancouver, BC, Canada. https://ieeexplore.ieee.org/document/6638947 https://doi.org/10.1109/ICASSP

  213. Park Y, Kellis M. Deep learning for regulatory genomics. Nat Biotechnol. 2015;33(8):825–6.

    Article  CAS  PubMed  Google Scholar 

  214. Bahdanau D, Cho K, Bengio Y. Neural machine translation by jointly learning to align and translate. In arXiv. preprint arXiv:14090473. 2014. https://arxiv.org/pdf/1409.0473.pdf

  215. Ragoza M, Hochuli J, Idrobo E, Sunseri J, Koes DR. Protein-ligand scoring with convolutional neural networks. J Chem Inf Model. 2017;57(4):942–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Gomes J, Ramsundar B, Feinberg NE, Pande V. Atomic convolutional networks for predicting protein-ligand binding affinity. 2017. In arXiv:1703.10603. https://arxiv.org/pdf/1703.10603.pdf

  217. Lamers S, Salemi M, McGrath M, Fogel G. Prediction of R5, X4, and R5X4 HIV-1 coreceptor usage with evolved neural networks. IEEE/ACM Trans Comput Biol Bioinform. 2008;5(2):291–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Resch W, Hoffman N, Swanstrom R. Improved success of phenotype prediction of the human immunodeficiency virus type 1 from envelope variable loop 3 sequence using neural networks. Virology. 2001;288(1):51–62.

    Article  CAS  PubMed  Google Scholar 

  219. Sun T, Zhou B, Lai L, Pei J. Sequence-based prediction of protein protein interaction using a deep-learning algorithm. BMC Bioinformatics. 2017;18(1):277.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Wang S, Peng J, Ma J, Xu J. Protein secondary structure prediction using deep convolutional neural fields. Sci Rep. 2016;6:18962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Luong JH, Bouvrette P, Male KB. Developments and applications of biosensors in food analysis. Trends Biotechnol. 1997;15(9):369–77.

    Article  CAS  PubMed  Google Scholar 

  222. Yu D, Blankert B, Viré JC, Kauffmann JM. Biosensors in drug discovery and drug analysis. Anal Lett. 2005;38(11):1687–701.

    Article  CAS  Google Scholar 

  223. Cooper MA. Optical biosensors in drug discovery. Nat Rev Drug Discov. 2002;1(7):515–28.

    Article  CAS  PubMed  Google Scholar 

  224. Vigneshvar S, Sudhakumari CC, Senthilkumaran B, Prakash H. Recent advances in biosensor technology for potential applications – an overview. Front Bioeng Biotechnol. 2016;4:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Keusgen M. Biosensors: new approaches in drug discovery. Naturwissenschaften. 2002;89(10):433–44.

    Article  CAS  PubMed  Google Scholar 

  226. Zhang J, Zhang L. Nanostructures for surface plasmons. Adv Opt Photon. 2012;4(2):157–321.

    Article  CAS  Google Scholar 

  227. Pitarke JM, Silkin VM, Chulkov EV, Echenique PM. Theory of surface plasmons and surface-plasmon polaritons. Rep Prog Phys. 2007;70(1):1.

    Article  CAS  Google Scholar 

  228. Tang Y, Zeng X, Liang J. Surface plasmon resonance: an introduction to a surface spectroscopy technique. J Chem Educ. 2010;87(7):742–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Kretschmann E. Decay of non radiative surface plasmons into light on rough silver films. Comparison of experimental and theoretical results. Opt Commun. 1972;6(2):185–7.

    Article  Google Scholar 

  230. Rich RL, Myszka DG. Spying on HIV with SPR. Trends Microbiol. 2003;11(3):124–33.

    Article  CAS  PubMed  Google Scholar 

  231. Cormier EG, Persuh M, Thompson DA, Lin SW, Sakmar TP, Olson WC, et al. Specific interaction of CCR5 amino-terminal domain peptides containing sulfotyrosines with HIV-1 envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 2000;97(11):5762–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Hoffman TL, Canziani G, Jia L, Rucker J, Doms RW. A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 Env to chemokine receptors. Proc Natl Acad Sci U S A. 2000;97(21):11215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Misumi S, Nakajima R, Takamune N, Shoji S. A cyclic dodecapeptide-multiple-antigen peptide conjugate from the undecapeptidyl arch (from Arg(168) to Cys(178)) of extracellular loop 2 in CCR5 as a novel human immunodeficiency virus type 1 vaccine. J Virol. 2001;75(23):11614–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Stenlund P, Babcock GJ, Sodroski J, Myszka DG. Capture and reconstitution of G protein-coupled receptors on a biosensor surface. Anal Biochem. 2003;316(2):243–50.

    Article  CAS  PubMed  Google Scholar 

  235. Brigham-Burke M, Edwards JR, O’Shannessy DJ. Detection of receptor-ligand interactions using surface plasmon resonance: model studies employing the HIV-1 gp120/CD4 interaction. Anal Biochem. 1992;205(1):125–31.

    Article  CAS  PubMed  Google Scholar 

  236. Cormier EG, Tran DN, Yukhayeva L, Olson WC, Dragic T. Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes. J Virol. 2001;75(12):5541–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Zhao H, Gorshkova II, Fu GL, Schuck P. A comparison of binding surfaces for SPR biosensing using an antibody-antigen system and affinity distribution analysis. Methods (San Diego, Calif). 2013;59(3):328–35.

    Article  CAS  Google Scholar 

  238. Gu L, Sims B, Krendelchtchikov A, Tabengwa E, Matthews QL. Differential binding of the HIV-1 envelope to phosphatidylserine receptors. Biochim Biophys Acta Biomembr. 2017;1859(10):1962–6.

    Article  CAS  PubMed  Google Scholar 

  239. Hijazi K, Wang Y, Scala C, Jeffs S, Longstaff C, Stieh D, et al. DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4. PLoS One. 2011;6(12):e28307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Martin-Garcia J, Cocklin S, Chaiken IM, Gonzalez-Scarano F. Interaction with CD4 and antibodies to CD4-induced epitopes of the envelope gp120 from a microglial cell-adapted human immunodeficiency virus type 1 isolate. J Virol. 2005;79(11):6703–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Prigent J, Jarossay A, Planchais C, Eden C, Dufloo J, Kök A, et al. Conformational plasticity in broadly neutralizing HIV-1 antibodies triggers polyreactivity. Cell Rep. 2018;23(9):2568–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Derking R, Ozorowski G, Sliepen K, Yasmeen A, Cupo A, Torres JL, et al. Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLoS Pathog. 2015;11(3):e1004767.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  243. Xu L, Pegu A, Rao E, Doria-Rose N, Beninga J, McKee K, et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science. 2017;358(6359):85–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Badamchi-Zadeh A, Tartaglia LJ, Abbink P, Bricault CA, Liu P-T, Boyd M, et al. Therapeutic efficacy of vectored PGT121 gene delivery in HIV-1-infected humanized mice. J Virol. 2018;92(7):e01925–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Lorin V, Malbec M, Eden C, Bruel T, Porrot F, Seaman MS, et al. Broadly neutralizing antibodies suppress post-transcytosis HIV-1 infectivity. Mucosal Immunol. 2017;10(3):814–26.

    Article  CAS  PubMed  Google Scholar 

  246. Ahmed FE, Wiley JE, Weidner DA, Bonnerup C, Mota H. Surface Plasmon Resonance (SPR) spectrometry as a tool to analyze nucleic acid–protein interactions in crude cellular extracts. Cancer Genomics Proteomics. 2010;7(6):303–9.

    CAS  PubMed  Google Scholar 

  247. Geuijen KPM, Oppers-Tiemissen C, Egging DF, Simons PJ, Boon L, Schasfoort RBM, et al. Rapid screening of IgG quality attributes – effects on Fc receptor binding. FEBS Open Bio. 2017;7(10):1557–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Shah NB, Duncan TM. Bio-layer interferometry for measuring kinetics of protein-protein interactions and allosteric ligand effects. J Vis Exp. 2014;18(84):e51383.

    Google Scholar 

  249. McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, et al. Holes in the glycan shield of the native HIV envelope are a target of trimer-elicited neutralizing antibodies. Cell Rep. 2016;16(9):2327–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Dennison SM, Anasti KM, Jaeger FH, Stewart SM, Pollara J, Liu P, et al. Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. J Virol. 2014;88(16):9406–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  251. Dubrovskaya V, Guenaga J, de Val N, Wilson R, Feng Y, Movsesyan A, et al. Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response. PLoS Pathog. 2017;13(9):e1006614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  252. Chabot DJ, Chen H, Dimitrov DS, Broder CC. N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates. J Virol. 2000;74(9):4404–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Yen P-J, Herschhorn A, Haim H, Salas I, Gu C, Sodroski J, et al. Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. J Virol. 2014;88(9):5014–28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  254. Ozorowski G, Pallesen J, de Val N, Lyumkis D, Cottrell CA, Torres JL, et al. Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike. Nature. 2017;547(7663):360–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Ingale J, Wyatt RT. Kinetic analysis of monoclonal antibody binding to HIV-1 gp120-derived hyperglycosylated cores. Bio Protoc. 2015;5(20):e1615.

    PubMed  Google Scholar 

  256. Fera D, Schmidt AG, Haynes BF, Gao F, Liao HX, Kepler TB, et al. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Proc Natl Acad Sci U S A. 2014;111(28):10275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Kumar R, Ozorowski G, Kumar V, Holden LG, Shrivastava T, Patil S, et al. Characterization of a stable HIV-1 B/C recombinant, soluble and trimeric envelope glycoprotein (Env) highly resistant to CD4-induced conformational changes. J Biol Chem. 2017;292(38):15849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Petersen RL. Strategies using bio-layer interferometry biosensor technology for vaccine research and development. Biosensors (Basel). 2017;7(4):49.

    Article  CAS  Google Scholar 

  259. Broussard JA, Green KJ. Research techniques made simple: methodology and applications of Förster Resonance Energy Transfer (FRET) microscopy. J Investig Dermatol. 2017;137(11):e185–e91.

    Article  CAS  PubMed  Google Scholar 

  260. Piston DW, Kremers G-J. Fluorescent protein FRET: the good, the bad and the ugly. Trends Biochem Sci. 2007;32(9):407–14.

    Article  CAS  PubMed  Google Scholar 

  261. Ha T, Ting AY, Liang J, Caldwell WB, Deniz AA, Chemla DS, et al. Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism. Proc Natl Acad Sci. 1999;96(3):893–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Shrestha D, Jenei A, Nagy P, Vereb G, Szöllősi J. Understanding FRET as a research tool for cellular studies. Int J Mol Sci. 2015;16(4):6718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Schuler B, Lipman EA, Eaton WA. Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy. Nature. 2002;419(6908):743–7.

    Article  CAS  PubMed  Google Scholar 

  264. Hofmann H, Hillger F, Pfeil SH, Hoffmann A, Streich D, Haenni D, et al. Single-molecule spectroscopy of protein folding in a chaperonin cage. Proc Natl Acad Sci. 2010;107(26):11793–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Cole GB, Reichheld SE, Sharpe S. FRET analysis of the promiscuous yet specific interactions of the HIV-1 Vpu transmembrane domain. Biophys J. 2017;113(9):1992–2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. Takagi S, Momose F, Morikawa Y. FRET analysis of HIV-1 Gag and GagPol interactions. FEBS Open Bio. 2017;7(11):1815–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Schroeder S, Kaufman JD, Grunwald M, Walla PJ, Lakomek NA, Wingfield PT. HIV-1 gp41 transmembrane oligomerization monitored by FRET and FCS. FEBS Lett. 2018;592(6):939–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. Sharma KK, Przybilla F, Restle T, Godet J, Mely Y. FRET-based assay to screen inhibitors of HIV-1 reverse transcriptase and nucleocapsid protein. Nucleic Acids Res. 2016;44(8):e74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  269. Ma X, Lu M, Gorman J, Terry DS, Hong X, Zhou Z, et al. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. elife. 2018;7:e34271.

    Article  PubMed  PubMed Central  Google Scholar 

  270. Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science. 2014;346(6210):759–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Stockmann H, Todorovic V, Richardson PL, Marin V, Scott V, Gerstein C, et al. Cell-surface receptor-ligand interaction analysis with homogeneous time-resolved FRET and metabolic glycan engineering: application to transmembrane and GPI-anchored receptors. J Am Chem Soc. 2017;139(46):16822–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

MG was supported by an RMIT PhD Scholarship. The authors thank Dr Andrew Guy, School of Science, RMIT University for his helpful input and discussions on the machine learning section of this chapter.

Author information

Authors and Affiliations

  1. School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia

    Jacqueline K. Flynn

  2. School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia

    Jacqueline K. Flynn, Matthew Gartner & Paul R. Gorry

  3. Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia

    Jacqueline K. Flynn & Annamarie Laumaea

Authors
  1. Jacqueline K. Flynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Gartner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annamarie Laumaea
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul R. Gorry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacqueline K. Flynn .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, University of South Florida, Tampa, FL, USA

    Paul Shapshak

  2. Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India

    Seetharaman Balaji

  3. Biomedical Informatics 17, Irulan Sandy Annex, Pondicherry, Pondicherry, India

    Pandjassarame Kangueane

  4. Oral Biology and Medicine, CHS 63-090, UCLA School of Dentistry Oral Biology and Medicine, CHS 63-090, Los Angeles, CA, USA

    Francesco Chiappelli

  5. Department of Internal Medicine, University of South Florida, Tampa, FL, USA

    Charurut Somboonwit

  6. Department of Internal Medicine, University of South Florida, Tampa, FL, USA

    Lynette J. Menezes

  7. Department of Internal Medicine, University of South Florida, Tampa, FL, USA

    John T. Sinnott

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Flynn, J.K., Gartner, M., Laumaea, A., Gorry, P.R. (2019). Futuristic Methods for Determining HIV Co-receptor Use. In: Shapshak, P., et al. Global Virology III: Virology in the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-030-29022-1_23

Download citation

Publish with us

Policies and ethics

Search

Navigation