Low-Dose Oral Type I Interferons Reduce Early Virus Replication of Murine Cytomegalovirus In Vivo

Abstract

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-α and IFN-β) 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 × 10⁴ pfu per mouse [0.6 LD₅₀] and 2 × 10^4.12 pfu per mouse [0.8 LD₅₀]). Analysis of IFN retention, using [³⁵S]-labeled IFN-αl compared with the nonreceptor binding mutant IFN-αl (R33M) administered orally to mice, revealed binding of wild-type IFN-αl to several tissues. In particular, IFN was retained by tissues proximal to lymphoid regions, including the posterior nasal cavity, posterior tongue, small intestine, and rectum. These findings suggest that type I IFNs may inhibit MCMV replication by distal binding of the orally administered IFN to various tissues, which in turn augment the primary immune response to virus infection.