A MOUSE-ATTENUATED ENVELOPE PROTEIN VARIANT OF MURRAY VALLEY ENCEPHALITIS-VIRUS WITH ALTERED FUSION ACTIVITY

A neutralization escape variant of Murray Valley encephalitis virus (M VE), of low neuroinvasiveness in mice and with low haemagglutination a ctivity, had a reduced rate of replication in cultured cells during th e early phase of infection compared to wild-type MVE, The variant was internalized by Vero cells at a similar rate to wild-type MVE at pH 7. 4, but had reduced pH-dependent membrane fusion activity, In fusion-fr om-within experiments in infected mosquito (C6/36) cells, the variant had a lowered pH threshold for induction of fusion, which occurred at a reduced rate and to a lesser extent than for wild-type virus, Fusion was inhibited by monoclonal antibodies specific for envelope protein epitopes E-5 and E-8, which were implicated as determinants of fusion, These observations are discussed in relation to the regulation of MVE replication by fusion of the viral envelope with endosome membranes a nd, in turn, how rates of replication may affect neuroinvasion.