Effects of virally expressed interleukin-10 on vaccinia virus infection in mice
AuthorsKurilla, Michael G.
Welsh, Raymond M.
Kieff, Elliott D.
Brutkiewicz, Randy R.
KeywordsAnimals; *Cytotoxicity, Immunologic; Drug Administration Routes; Interleukin-10; Killer Cells, Natural; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Recombinant Proteins; Spleen; T-Lymphocytes, Cytotoxic; Vaccinia; Vaccinia virus
Medicine and Health Sciences
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AbstractTo investigate the in vivo role of interleukin-10 (IL-10) in viral infection, 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-beta gal) in normal and severe combined immunodeficient mice. In normal mice, VV-IL10 infection resulted in less natural killer cell activity at 3 days postinfection and less VV-specific cytotoxic T-cell activity at 6 or 7 days postinfection than VV-beta gal infection. However, the use of dermal scarification or intraperitoneal, intranasal, or intracerebral inoculation into immunocompetent mice resulted in no difference between VV-IL10 and VV-beta gal in visible lesions, mortality, protective immunity to a 100-fold lethal VV challenge, or VV-specific antibody response. In the immunodeficient mice, VV-IL10 infection resulted in greater natural killer cell activity and lower virus replication than VV-beta gal infection. These in vivo effects were subtler and more complex than had been anticipated. From the VV-IL10 murine 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.
J Virol. 1993 Dec;67(12):7623-8.