Herpes simplex virus entry is associated with tyrosine phosphorylation of cellular proteins

The initial step in herpes simplex virus (HSV) entry is binding of Virion g lycoprotein (g)C and/or gB to cell surface heparan sulfate. After this init ial attachment, go interacts with cell surface receptor or receptors, and t he virion envelope fuses with the cell membrane. Fusion requires Viral glyc oproteins gB, gD, gL, and gH, but the cellular factors that participate in or the pathways activated by viral entry have not been defined. To determin e whether signal transduction pathways are triggered by viral-cell fusion, we examined the association of viral entry with tyrosine phosphorylation of cellular proteins. Using immunoprecipitation and Western blotting, we foun d that at least three cytoplasmic host cell proteins, designated p80, p104, and p140, become tyrosine phosphorylated within 5-10 min after exposure to HSV-1 or HSV-2. However, no phosphorylation is detected when cells are exp osed to a mutant virus deleted in gL that binds but fails to penetrate. Pho sphorylation is restored when the gL-deletion virus is grown on a complemen ting cell line. Viral entry and the phosphorylation of p80, p104, and p140 are inhibited when cells are infected with virus in the presence of protein tyrosine kinase inhibitors, Taken together, these studies suggest that tyr osine phosphorylation of host cellular proteins is triggered by viral entry . (C) 1999 Academic Press.