Cell fusion activities of HSV-1 and HSV-2 gD mutants with target BHK-95-19 cells expressing HVEM, nectin-1, or nectin-2. Through complex multistep processes the virus is able to infect host cells through this usage various cellular proteins and structures. The alphaherpesviruses have a very broad host range in cultured cells and can infect and cause diseases in selected laboratory animals, such as rodents (41). Furthermore, HSV-1 infection of human primary cells expressing both HVEM and PILRα was blocked by either anti-PILRα or anti-HVEM antibody. There are common themes as well as intriguing differences in the entry mechanisms of herpes simplex virus into ocular cells. In addition to supporting HSV-1 entry, gD receptors also support HSV-1 cell-to-cell spread (8, 41). While CV-N treated virions were significantly deficient in entering into cells, HSV-1 glycoproteins-expressing cells pretreated with CV-N demonstrated reduced cell-to-cell fusion and polykaryocytes formation.
Lastly, the fusogenic activities of the glycoproteins in the viral envelope are not dependent on a set of unique interactions between glycoprotein D and its receptor. Abbreviations: gB, gD, gH, and gL, glycoproteins B, D, H, and L, respectively; HSV, herpes simplex virus; HVEM, herpesvirus entry mediator; 3-OST, 3-O-sulfotransferase; 3-O-S HS, 3-O-sulfated heparan sulfate; CHO, Chinese hamster ovary; BHK, baby hamster kidney; β-gal, β-galactosidase; HRP, horseradish peroxidase. Because extreme selective pressure was required to favor these mutations and such mutations are rare in clinical isolates, the wild-type forms of gC and gK must provide for optimal viral replication and propagation in cell culture as well asin vivo,despite the view that gC is dispensable in cultured cells. We conclude that although undefined factors unique to individual wild-type HSV-1 laboratory strains affect entry kinetics, entry of any one strain is greatly influenced by interactions of virus with specific cell components during at least two distinct phases of attachment before penetration. Moreover, the second phase to stabilize binding seems to be the rate-limiting event in entry. Since major differences in the amounts or sulfation patterns of heparan sulfate were not detected, differences in the surfaces of HEp-2 and Vero cells that influence the kinetics and efficiency of HSV-1 entry are likely in the fine structure of heparan sulfate or in the presence and quantity of other unidentified receptors.