Protection against lethal Venezuelan equine encephalitis (VEE) virus infection by cell-free supernatant obtained from...

Considerable effort has been directed at unraveling the mechanisms underlying protection and recovery in acute viral infections. Various factors, including antibody, interferon, lymphokines and certain lymphocyte and macrophage cell constituents, have been shown to play a role in host recovery. We have previously studied an adoptive transfer system in experimental VEE virus CNS infection in a mouse model, and shown that both T cells and B cells exert an influence in protecting the host from lethal CNS infection with this virus. Because of the complexity involved in the adoptive transfer of protection, we sought a simpler and more easily defined experimental approach to dissect the various factors responsible for protection in our model. We here report that immune cell-free supernatant, derived from mice immunized with vaccine against VEE virus, exerts as much protection as the whole cell transfer system against lethal VEE virus infection. Such cell-free supernatant allowed us to look more closely at individual host immune factors in their relationship to protection against infection. Studies herein reported demonstrate that the protection conferred by immune cell-free supernatants is not dependent on neutralizing antibody or interferon, but rather appears to be related to the presence of both interleukin-1 and -2 and the activation and potentiation of NK cell activity against VEE virus.