Cell entry mechanisms of HSV: what we have learned in recent years

Abstract

HSV type-1 and -2 are widespread pathogens producing lifelong infection with multiple sequelae, including oral, ocular and genital disease. The process of herpesvirus entry is a highly complex process involving numerous viral and cellular factors. Entry begins with attachment of virus to the cell surface followed by interactions between viral glycoproteins and cellular receptors to facilitate capsid penetration. The nucleocapsid is then transported along microtubules to the nuclear membrane, where viral DNA is released for replication in the nucleus. The work reviewed here comprises the most recent advancements in our understanding of the mechanism involved in the herpesvirus entry process.

Keywords: HSV; attachment; cell-to-cell spread; endocytosis; entry; fusion; glycoproteins; herpesviruses.

Figure 1. Molecular interactions mediating HSV entry

Initial attachment to cells is facilitated by binding of HSPGs by HSV glycoproteins gC and/or gB. Virions are then transported along cellular filopodia toward the cell body in a process termed viral surfing. Recruitment of a fusion complex comprising gB, gD and gH/gL is initiated by gD binding to one of its receptors, nectin-1, herpes virus entry mediator or 3-O-sulfated heparan sulfate. Binding of gB to one of its receptors, PILRα, NMHC-IIA or MAG, is then required for delivery of the viral nucleocapsid to the cytoplasm, accomplished either by membrane fusion or endocytosis/phagocytosis-like uptake. 3-OS HS: 3-O-sulfated heparan sulfate; HVEM: Herpes virus entry mediator.