Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Virology. 2024 Aug;596:110120. doi: 10.1016/j.virol.2024.110120. Epub 2024 May 23.
Glycoprotein C (gC), one of ∼12 HSV-1 envelope glycoproteins, carries out several important functions during infection, including the enhancement of virion attachment by binding to host cell heparan sulfate proteoglycans (HSPG). Here we report that gC can also enhance the release of cell-free progeny virions at the end of the infectious cycle. This activity was observed in multiple cellular contexts including Vero cells and immortalized human keratinocytes. In the absence of gC, progeny virions bound more tightly to infected cells, suggesting that gC promotes the detachment of virions from the infected cell surface. Given this finding, we analyzed the biochemical interactions that tether progeny virions to cells and report evidence for two distinct modes of binding. One is consistent with a direct interaction between gC and HSPG, whereas the other is gC-independent and likely does not involve HSPG. Together, our results i) identify a novel function for a long-studied HSV-1 glycoprotein, and ii) demonstrate that the extracellular release of HSV-1 virions is a dynamic process involving multiple viral and host components.
糖蛋白 C（gC）是约 12 种单纯疱疹病毒 1 型包膜糖蛋白之一，在感染过程中发挥多种重要功能，包括通过与宿主细胞硫酸乙酰肝素蛋白聚糖（HSPG）结合增强病毒粒子的附着。在这里，我们报告 gC 还可以增强感染周期结束时无细胞的子代病毒粒子的释放。这种活性在包括 Vero 细胞和永生化人角质形成细胞在内的多种细胞环境中都观察到。在没有 gC 的情况下，子代病毒粒子与感染细胞的结合更紧密，这表明 gC 促进了病毒粒子从感染细胞表面的脱离。鉴于这一发现，我们分析了将子代病毒粒子与细胞连接的生化相互作用，并报告了两种不同结合模式的证据。一种与 gC 和 HSPG 之间的直接相互作用一致，而另一种与 gC 无关，可能不涉及 HSPG。总之，我们的结果 i）确定了一种长期研究的单纯疱疹病毒 1 型糖蛋白的新功能，ii）表明单纯疱疹病毒 1 型病毒粒子的细胞外释放是一个涉及多种病毒和宿主成分的动态过程。
