ROLE OF THE VACCINIA VIRUS E3L AND K3L GENE-PRODUCTS IN RESCUE OF VSVAND EMCV FROM THE EFFECTS OF IFN-ALPHA

Vaccinia virus (VV) has been shown to be relatively resistant to the a ntiviral effects of interferon-alpha (IFN-alpha) and to rescue replica tion of IFN-sensitive viruses, such as encephalomyocarditis virus (EMC V) and vesicular stomatitis virus (VSV), from the antiviral effects of IFN. The E3L and K3L gene products have been implicated in the IFN re sistance of VV. We have investigated the role that these VV-encoded fu nctions play in the rescue of VSV and EMCV from the effects of IFN, Tr ansient expression of the E3L open reading frame (ORF) was sufficient to rescue VSV but not EMCV from the IFN-induced antiviral state. Rescu e of VSV by mutants of E3L correlated with the ability of the mutated E3L gene products to bind dsRNA, Conversely, transient expression of t he K3L ORF was sufficient to partially rescue EMCV but not VSV from th e effects of IFN, Results with VV deleted of either the K3L or E3L ORF s were consistent with results obtained by transient expression of the se genes. These results demonstrate that the VV E3L gene products are likely responsible for the VV-mediated rescue of VSV from the effects of IFN and the K3L gene product is likely at least partly responsible for rescue of EMCV.