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Herpes simplex virus type 1 modulates cellular gene expression during quiescent infection of neuronal cells

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Abstract

Gene expression profiling of neuronally-differentiated (ND)-PC12 cells quiescently infected (QIF) with herpes simplex virus type 1 (HSV-1) was performed to determine the response of neuronal cells to long-term maintenance of a non-replicating viral genome independent of the heterogeneous response that occurs in latently infected ganglia. Quiescent infections were characterized by 606 up-regulated and 821 down-regulated cellular genes (P < 0.005) compared to parallel, identically treated, mock-infected cultures. Gene ontology analyses suggested that up-regulated cellular genes were involved in steroid biosynthesis and mitogen-activated protein kinase signaling pathways and significantly overrepresented for transcription factor and transcription regulatory functions. Many of the most up-regulated cellular genes encode for proteolytic enzymes involved in neurite outgrowth/axon remodeling. Genes involved in DNA and nucleotide metabolism and apoptosis tended to be down-regulated. These findings demonstrate that a quiescent HSV-1 infection significantly alters neuronal gene expression in ways that may promote survival of the host cell and maintenance of latency.

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Acknowledgments

We thank Michael Killen for providing technical assistance, and Dr. Kevin Becker, Dr. Kuey-Chu Chen, Dr. Robert Jacob, and Dr. Jeff Ebersole for helpful discussions. This research was supported by grants from the National Institute of Health DE014142 (CSM), P20 RR16481 (AJS), and the Microarray Facility Pilot Program at the University of Kentucky (CSM).

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Authors and Affiliations

  1. Department of Microbiology, Immunology and Molecular Genetics, Center for Oral Health Research, MN 324, University of Kentucky, College of Dentistry and College of Medicine, Chandler Medical Center, 800 Rose Street, Lexington, KY, 40536-0297, USA

    Robert J. Danaher, Brandon S. McGarrell & Craig S. Miller

  2. Department of Statistics, College of Arts and Sciences, University of Kentucky, Lexington, KY, 40536-0297, USA

    Arnold J. Stromberg

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  1. Robert J. Danaher
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  2. Brandon S. McGarrell
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  4. Craig S. Miller
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Correspondence to Craig S. Miller.

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Danaher, R.J., McGarrell, B.S., Stromberg, A.J. et al. Herpes simplex virus type 1 modulates cellular gene expression during quiescent infection of neuronal cells. Arch Virol 153, 1335–1345 (2008). https://doi.org/10.1007/s00705-008-0122-x

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  • DOI: https://doi.org/10.1007/s00705-008-0122-x

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