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.