Herpes simplex virus type 1 entry through a cascade of virus-cell interactions requires different roles of gD and gH in penetration

Abstract

We examined the entry process of herpes simplex virus type 1 (HSV-1) by using infectious virus and previously characterized noninfectious viruses that can bind to cells but cannot penetrate as a result of inactivation of essential viral glycoprotein D (gD) or H (gH). After contact of infectious virus with the cell plasma membrane, discernible changes of the envelope and tegument could be seen by electron microscopy. Noninfectious virions were arrested at distinct steps in interactions with cells. Viruses inactivated by anti-gD neutralizing antibodies attached to cells but were arrested prior to initiation of a visible fusion bridge between the virus and cell. As judged from its increased sensitivity to elution, virus lacking gD was less stably bound to cells than was virus containing gD. Moreover, soluble gD could substantially reduce virus attachment when added to cells prior to or with the addition of virus. Virus inactivated by anti-gH neutralizing antibodies attached and could form a fusion bridge but did not show expansion of the fusion bridge or extensive rearrangement of the envelope and tegument. We propose a model for infectious entry of HSV-1 by a series of interactions between the virion envelope and the cell plasma membrane that trigger virion disassembly, membrane fusion, and capsid penetration. In this entry process, gD mediates a stable attachment that is likely required for penetration, and gH seems to participate in fusion initiation or expansion.

Mechanisms by Which Ambient Humidity May Affect Viruses in Aerosols

“…The herpes simplex virus is an exemplar. Early studies using HEp-2 and Vero cells indicated that penetration of cells by herpes simplex virus can be initiated by receptor binding and pH-neutral fusion with the cell surface (15,62); however, more-recent studies reported another major pathway by endocytosis that requires low pH using HeLa and Chinese hamster ovary cells (33,37). This sensitivity may confound the relationship with RH for viruses whose entry pathway depends on the host cell.…”

Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways

“…Productive infection with alphaherpesviruses had been thought to be established only by direct fusion of the viral envelope with the plasma membrane, as demonstrated by electron microscopic analysis and the effects of treatment with neutralizing antibodies (Fuller and Spear, 1987;Fuller et al, 1989;Fuller and Lee, 1992). Agents that perturb endocytosis were found to have little or no effect on herpes simplex virus (HSV) infection in HEp-2 and Vero cells (Wittels and Spear, 1991).…”

Characterization of a novel third member of the human cytomegalovirus glycoprotein H-glycoprotein L complex

“…These two envelope glycoproteins, which associate to form the gH-gL complex, have been implicated as key participants in fusion events critical to herpesvirus life cycles. Specifically, the gH-gL complex participates in both the pH-independent fusion of the viral envelope with the host cell plasma membrane and the cell-to-cell spread of virus (8,10,12,13,21,24,26,27). Studies of the human cytomegalovirus (HCMV) gH and gL proteins have shown that they are representative gH and gL homologs.…”