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J Virol. Jan 1996; 70(1): 612–616.
PMCID: PMC189854

The v-erbB oncogene confers enhanced cellular susceptibility to reovirus infection.

Abstract

We have previously demonstrated that two mouse cell lines that are poorly 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). This enhancement of infection efficiency requires a functional EGFR, since such an enhancement is not observed in cells expressing a mutated (kinase-inactive) EGFR. The additional finding that reovirus is capable of directly binding to the N-terminal ectodomain of the EGFR (D. Tang, 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 activation of a signalling cascade that somehow augments the ensuing infection process. In the present study, we address this question, using cells transfected with the v-erbB oncogene, which encodes a protein structurally related to the EGFR but lacking a large portion of the N-terminal ligand-binding domain. The v-erbB protein also possesses ligand-independent, 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 assayed for their susceptibilities to reovirus infection. Infectivity was determined by immunofluorescent detection of viral proteins, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of radiolabeled cells, and plaque titration. All three assays demonstrated a drastically higher degree of susceptibility to infection in the THC-11 cell line. This enhanced susceptibility was found to be abrogated by treatment of the cells with genistein, an inhibitor of tyrosine protein kinases, but only partially by treatment with daidzein, an inactive analog of genistein. We propose that the mechanism of enhancement of infection efficiency conferred by EGFR and v-erbB is through the opportunistic utilization by the virus of an already activated signal transduction pathway.

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Selected References

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