LOW-DOSE ORAL TYPE-I INTERFERONS REDUCE EARLY VIRUS-REPLICATION OF MURINE CYTOMEGALOVIRUS IN-VIVO

Immunity to viral infections involves both innate and antigen-specific immune responses, The antiviral properties of interferons (IFNs) are part of the innate immune response. Low doses of type I IFNs (IFN-alph a and IFN-beta) administered daily (10 IU per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected susceptible BALB /c mice, Significant inhibition of virus replication was observed for two different inoculum doses of virus (2 x 10(4) pfu per mouse [0.6 LD 50] and 2 x 10(4.12) pfu per mouse [0.8 LD50]) Analysis of IFN retenti on, using [S-35]-labeled IFN-alpha 1 compared with the nonreceptor bin ding mutant IFN-alpha 1 (R33M) administered orally to mice, revealed b inding of wild-type IFN-alpha 1 to several tissues, In particular, IFN was retained by tissues proximal to lymphoid regions, including the p osterior nasal cavity, posterior tongue, small intestine, and rectum, These findings suggest that type I IFNs may inhibit MCMV replication b y distal binding of the orally administered IFN to various tissues, wh ich in turn augment the primary immune response to virus infection.