THE V-ERBB ONCOGENE CONFERS ENHANCED CELLULAR-SUSCEPTIBILITY TO REOVIRUS INFECTION

We have previously demonstrated that two mouse cell lines that are poo rly infectible by reovirus become highly susceptible upon transfection with the gene encoding the epidermal growth factor receptor (EGFR) (J . E. Strong, D. Tang, and P. W. K. Lee, Virology 197:405-411, 1993). T his enhancement of infection efficiency requires a functional EGFR, si nce such an enhancement is not observed in cells expressing a mutated (kinase-inactive) EGFR. The additional finding that reovirus is capabl e of directly binding to the N-terminal ectodomain of the EGFR (D. Tan g, J. E. Strong, and P. W. K. Lee, Virology 197:412-414, 1993) has led us to question whether this interaction is required for the activatio n of a signalling cascade that somehow augments the ensuing infection process. In the present study, rye address this question, using cells transfected with the v-erbB oncogene, which encodes a protein structur ally related to the EGFR but lacking a large portion of the N-terminal ligand-binding domain. The v-erbB protein also possesses Ligand-indep endent, constitutive tyrosine kinase activity. Control NIH 3T3 cells, which are poorly infectible by reovirus (serotype 3, strain Dearing), and NIH 3T3 cells transfected with the v-erbB oncogene (THC-11) were a ssayed for their susceptibilities to reovirus infection. Infectivity w as determined by immunofluorescent detection of viral proteins, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of radiol abeled cells, acid plaque titration. All three assays demonstrated a d rastically higher degree of susceptibility to infection in the THC-11 cell line. This enhanced susceptibility was found to be abrogated by t reatment of the cells with genistein, an inhibitor of tyrosine protein kinases, but only partially by treatment with daidzein, an inactive a nalog of genistein. We propose that the mechanism of enhancement of in fection efficiency conferred by EGFR and v-erbB is through the opportu nistic utilization by the virus of an already activated signal transdu ction pathway.