Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox

Genetic resistance to clinical mousepox (ectromelia virus) varies among inb red laboratory mice and is characterized by an effective natural killer (NK ) response and the early onset of a strong CD8(+) cytotoxic T-lymphocyte (C TL) response in resistant mice. We have investigated the influence of virus expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-po sitive ectromelia virus suppressed cytolytic responses of NK and CTL and th e expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4 expressing virus developed symptoms of acute mousepo x accompanied by high mortality, similar to the disease seen when genetical ly sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mou sepox. These data therefore suggest that virus-encoded IL-4 not only suppre sses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.