ANTIVIRAL ACTIVITIES OF INDIVIDUAL MURINE IFN-ALPHA SUBTYPES IN-VIVO - INTRAMUSCULAR INJECTION OF IFN EXPRESSION CONSTRUCTS REDUCES CYTOMEGALOVIRUS REPLICATION

The IFN-alpha cytokines belong to a multigene family, However, the in vivo biological functions of each of the IFN-alpha subtypes is unknown . Recently, we developed an experimental model in which the tibialis a nterior muscles of mice were transfected in situ with naked DNA plasmi ds encoding an IFN transgene, Here we use this model to investigate th e in vivo effect of the expression of three murine IFN-alpha subtypes (A1, A4, and A9) on murine CMV replication in C57BL/6, BALB/c, and A/J mice, CMV was shown to replicate in the tibialis anterior muscles of mice for at least 6 days and induced an inflammatory infiltrate, Howev er, mice expressing the IFN-alpha transgenes showed a marked reduction in the peak titers of virus replication, with less severe inflammatio n in the muscles compared with control mice that were inoculated with blank vectors, Moreover, mice expressing the IFN-alpha 1 transgene had significantly lower CMV titers in the inoculated muscle than mice exp ressing either the IFN-alpha 4 or the IFN-alpha 9 transgenes, Furtherm ore, IFN-alpha/beta receptor knockout mice had markedly higher levels of CMV replication in the tibialis anterior muscles than the wild-type parental strain (129/Sv/Ev) following IFN-alpha 1 transgene inoculati on, suggesting that the protection observed is due to host cell-mediat ed IFN signaling, These data provide the first evidence Indicating tha t there are in vivo differences in the antiviral efficacy of the IFN-a lpha subtypes.