Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry

Herpes simplex virus type-1 and type-2 are highly prevalent human pathogens causing life-long infections. The process of infection begins when the virions bind heparan sulfate moieties present on host cell surfaces. This initial attachment then triggers a cascade of molecular interactions involving multiple viral and host cell proteins and receptors, leading to penetration of the viral nucleocapsid and tegument proteins into the cytoplasm. The nucleocapsid is then transported to the nuclear membrane and the viral DNA is released for replication in the nucleus. Recent studies have revealed that herpes simplex virus entry or penetration into cells may be a highly complex process and the mechanism of entry may demonstrate unique cell-type specificities. Although specificities clearly exist, past and ongoing studies demonstrate that herpes simplex virus may share certain common receptors and pathways that are also used by many other human viruses. This minireview helps to shed light on recent revelations on the herpes simplex virus entry process.