Anti-retroviral effects of type I IFN subtypes in vivo

Type I IFN play a very important role in immunity against viral infections. Murine type I IFN belongs to a multigene family including 14 IFN-alpha subtypes but the biological functions of IFN-alpha subtypes in retroviral infections are unknown. We have used the Friend retrovirus model to determine the anti-viral effects of IFN-alpha subtypes in vitro and in vivo. IFN-alpha subtypes alpha 1, alpha 4, alpha 6 or alpha 9 suppressed Friend virus (FV) replication in vitro, but differed greatly in their anti-viral efficacy in vivo. Treatment of FV-infected mice with the IFN-alpha subtypes alpha 1, alpha 4 or alpha 9, but not alpha 6 led to a significant reduction in viral loads. Decreased splenic viral load after IFN-alpha 1 treatment correlated with an expansion of activated FV-specific CD8(+) T cells and NK cells into the spleen, whereas in IFN-alpha 4- and -alpha 9-treated mice it exclusively correlated with the activation of NK cells. The results demonstrate the distinct anti-retroviral effects of different IFN-alpha subtypes, which may be relevant for new therapeutic approaches.