EFFECTS OF VIRALLY EXPRESSED INTERLEUKIN-10 ON VACCINIA VIRUS-INFECTION IN MICE

To investigate the in vivo role of interleukin-10 (IL-10) in viral inf ection, we compared infections with a recombinant vaccinia virus (VV) expressing IL-10 (VV-IL10) under control of the VV P7.5 promoter and a control virus (VV-betagal) in normal and severe combined immunodefici ent mice. In normal mice, W-IL10 infection resulted in less natural ki ller cell activity at 3 days postinfection and less W-specific cytotox ic T-cell activity at 6 or 7 days postinfection than W-betagal infecti on. However, the use of dermal scarification or intraperitoneal, intra nasal, or intracerebral inoculation into immunocompetent mice resulted in no difference between VV-IL10 and VV-betagal in visible lesions, m ortality, protective immunity to a 100-fold lethal VV challenge, or VV -specific antibody response. In the immunodeficient mice, VV-IL10 infe ction resulted in greater natural killer cell activity and lower virus replication than W-betagal infection. These in vivo effects were subt ler and more complex than had been anticipated. From the VV-IL10 murin e model, the Epstein-Barr virus-encoded homolog of human IL-10, BCRF1, may provide a selective advantage by blunting the early human natural killer cell and cytotoxic T-cell responses so that Epstein-Barr virus can establish a well-contained latent infection in B lymphocytes.