Analysis of herpes simplex type 1 gB, gD, and gH/gL on production of infectious HIV-1: HSV-1 gD restricts HIV-1 by exclusion of HIV-1 Env from maturing viral particles
Analysis of herpes simplex type 1 gB, gD, and gH/gL on production of infectious HIV-1: HSV-1 gD restricts HIV-1 by exclusion of HIV-1 Env from maturing viral particles
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DOI：
10.1186/s12977-019-0470-5
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发表时间：
2019-04-02
期刊：
影响因子：
3.3
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.
我们之前的研究表明，HSV-1的转基因可以限制传染性HIV-1从细胞中释放。在这项研究中，我们分析了四种HSV-1糖蛋白（gD、gB和gH/gL）是否限制了传染性HIV-1的释放，这四种糖蛋白是HSV-1进入所需的最低糖蛋白。结果四种糖蛋白中，gD和gH/gL对转染HIV-1感染分子克隆（NL4-3株）的细胞产生传染性HIV-1有抑制作用，而gB无明显影响。脉冲追踪分析表明，gD不影响gp160合成和加工gp120/gp41，也不影响gp120/gp41向细胞表面的转运，也不影响HIV-1颗粒从细胞表面的释放。我们的分析表明，gD被纳入HIV-1病毒颗粒中，而gp120/gp41被排除在释放的病毒颗粒中。gD的截断突变体表明，细胞质结构域是不需要的，但需要膜结合的gD来限制传染性HIV-1的释放。最后，表达gD的细胞系也能有效地限制感染性病毒的释放。结论由于gD能够将HIV-1 gp120/gp41排除在成熟病毒之外，因此它可能为破译Env整合到成熟病毒颗粒中的机制提供了有用的工具。
BackgroundWe previously showed that the gM of HSV-1 could restrict the release of infectious HIV-1 from cells. In this study, we analyzed if the four HSV-1 glycoproteins (gD, gB, and gH/gL), which are the minimum glycoproteins required for HSV-1 entry, restricted the release of infectious HIV-1.ResultsOf these four glycoproteins, gD and gH/gL restricted the production of infectious HIV-1 from cells transfected with an infectious molecular clone of HIV-1 (strain NL4-3) while gB had no significant effect. Pulse-chase analyses indicated that gD did not affect the biosynthesis and processing of gp160 into gp120/gp41, the transport of the gp120/gp41 to the cell surface, or the release of HIV-1 particles from the cell surface. Our analyses revealed that gD was incorporated into HIV-1 virus particles while gp120/gp41 was excluded from released virus particles. Truncated mutants of gD revealed that the cytoplasmic domain was dispensable but that a membrane bound gD was required for the restriction of release of infectious HIV-1. Finally, cell lines expressing gD also potently restricted the release of infectious virus.ConclusionsDue to its ability to exclude HIV-1 gp120/gp41 from maturing virus, gD may provide a useful tool in deciphering mechanisms of Env incorporation into maturing virus particles.