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 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.
Kurilla
M G
MG
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Swaminathan
S
S
Welsh
R M
RM
Kieff
E
E
Brutkiewicz
R R
RR
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004333:Drug Administration Routes; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D011994:Recombinant Proteins; D016753:Interleukin-10