Val193 and Phe195 of the γ134.5 protein of herpes simplex virus 1 are required for viral resistance to interferon-α/β

Abstract

Herpes simplex viruses (HSV) are resistant to the antiviral action of interferon. However, the underlying mechanisms are not well understood. In this report, we show that unlike that of wild-type HSV-1, replication of the γ134.5 null mutants was significantly inhibited by exogenous interferon-α in cells devoid of interferon-α/β genes. Using a series of γ134.5 deletion mutants, the domain required for interferon resistance was mapped to the region containing amino acids 146 to 263 in the γ134.5 protein. Interestingly, Val193Glu and Phe195Leu substitutions in the protein phosphatase 1 interacting motif of the γ134.5 protein rendered HSV-1 sensitive to interferon-α. Furthermore, γ134.5 null mutants were sensitive to interferon-α/β in PKR+/+ but not in PKR-/- mouse embryo fibroblasts. These findings provide evidence that the γ134.5 protein contributes to HSV-1 resistance to interferon-α/β by inhibiting PKR function. © 2001 Academic Press.