Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160
Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160
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DOI：
10.1128/jvi.01476-17
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发表时间：
2018-01-01
影响因子：
5.4
通讯作者：
Stephens, Edward B.
中科院分区：
文献类型：
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作者：
Arachchige, Sachith Polpitiya;Henke, Wyatt;Stephens, Edward B.
在复制过程中损害或关闭特定宿主细胞功能的病毒编码的蛋白质可用作探针以鉴定用于复制来自其他家族的病毒的潜在蛋白质/途径。我们从单纯疱疹病毒1型（HSV-1）中筛选了9种蛋白质，以增强或限制人类免疫缺陷病毒1型（HIV-1）复制。我们发现几种HSV-1蛋白（糖蛋白M [gM]，US 3和UL 24）有效地限制了HIV-1的复制。与减少病毒蛋白合成的UL 24和US 3不同，我们观察到HIV-1的gM限制通过干扰gp 160的加工和转运发生，导致从细胞释放的成熟gp 120/gp 41水平显著降低。最后，我们表明，HSV-1 gM突变体缺乏大部分的C-末端结构域（HA-gM[.345-473]）既不限制gp 160加工，也不释放感染性病毒。这些研究从异源病毒中鉴定出可以通过新途径限制病毒的蛋白质。重要性人类HIV-1感染导致艾滋病，其特征是CD 4（+）T细胞的丢失和对机会性感染的易感性增加。HIV-1和HSV-1均可感染中枢神经系统（CNS）的星形胶质细胞和小胶质细胞。因此，鉴定直接限制HIV-1或干扰HIV-1复制所需途径的HSV-1蛋白可能导致新的抗逆转录病毒策略。这项研究的结果表明，从HSV-1中选择的病毒蛋白可以有效地限制HIV-1。此外，我们的研究结果表明，HSV-1的gM蛋白通过干扰gp 160的加工及其掺入从细胞成熟的病毒中的新途径限制HIV-1。
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.