INFECTION OF HUMAN T-LYMPHOID-CELLS BY HUMAN HERPESVIRUS-6 IS BLOCKEDBY 2 UNRELATED PROTEIN-TYROSINE KINASE INHIBITORS, BIOCHANIN-A AND HERBIMYCIN

Human herpesvirus 6 is a T lymphotropic herpesvirus that causes exanth em subitum in infants and is considered a potential cofactor in AIDS e tiopathogenesis and progression owing to its in vivo and in vitro inte ractions with human immunodeficiency virus, We report that no differen ces in phosphorylation on tyrosine residues of cellular proteins were detectable at early times following HHV-6 infection in comparison to u ninfected cells, On the contrary, several cellular proteins appeared p hosphorylated on tyrosine at 24-48 hr postinfection, In addition, when tyrosine phosphorylation induced by HHV-6 infection was inhibited by the tyrosine kinase inhibitor biochanin A, the infection of HSB-2 cell s was also coordinately reduced, as judged by inhibition of cytopathic effect and by inhibition of early and late viral antigen expression, Similar results were obtained with a second unrelated tyrosine kinase inhibitor, herbimycin, The inhibitors seem to act at a late stage of t he viral infectious cycle, since neither viral binding nor internaliza tion were affected. Thus, our results indicate that HHV-6 infection le ads to the phosphorylation of protein tyrosine kinases, which may play a role in the course of viral infection, probably by participating in the cytopathic effect induced by the virus.