Elsevier

Virology

Volume 518, May 2018, Pages 414-422
Virology

pUL34 binding near the human cytomegalovirus origin of lytic replication enhances DNA replication and viral growth

https://doi.org/10.1016/j.virol.2018.03.017Get rights and content
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Highlights

  • UL34 binding sites are highly conserved in HCMV isolates.

  • UL34 binds to the viral genome during the replication cycle.

  • UL34 binding sites in the origin for lytic replication contribute to efficient viral and viral DNA replication.

  • UL34 interacts with IE2, UL44 and UL84.

Abstract

The human cytomegalovirus (HCMV) UL34 gene encodes sequence-specific DNA-binding proteins (pUL34) which are required for viral replication. Interactions of pUL34 with DNA binding sites represses transcription of two viral immune evasion genes, US3 and US9. 12 additional predicted pUL34-binding sites are present in the HCMV genome (strain AD169) with three binding sites concentrated near the HCMV origin of lytic replication (oriLyt). We used ChIP-seq analysis of pUL34-DNA interactions to confirm that pUL34 binds to the oriLyt region during infection. Mutagenesis of the UL34-binding sites in an oriLyt-containing plasmid significantly reduced viral-mediated oriLyt-dependent DNA replication. Mutagenesis of these sites in the HCMV genome reduced the replication efficiencies of the resulting viruses. Protein-protein interaction analyses demonstrated that pUL34 interacts with the viral proteins IE2, UL44, and UL84, that are essential for viral DNA replication, suggesting that pUL34-DNA interactions in the oriLyt region are involved in the DNA replication cascade.

Keywords

Human cytomegalovirus
UL34
Origin of lytic replication
ChIP-seq
DNA replication

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1

Current address: Center for Vaccines & Immunity, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Room WA 4104, Columbus, OH 43205, United States.