Journal
JOURNAL OF VIROLOGY
Volume 92, Issue 2, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01476-17
Keywords
UL24; US3; gM; glycoprotein transport; herpes simplex virus; human immunodeficiency virus; restriction
Categories
Funding
- NIH [R21 AI108391]
- NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH [24-4]
- NIH AIDS Reagent Program, Division of AIDS, NIAID [11446]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI108391] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM113117] Funding Source: NIH RePORTER
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Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/ gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[.345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4(+) T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell.
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