PATHOGENESIS OF MURINE GAMMAHERPESVIRUS-68 INFECTION IN INTERLEUKIN-6-DEFICIENT MICE

Murine gammaherpesvirus-68 (MHV-68) induces high levels of interleukin (IL)-6 production in both naive and primed lymphocyte populations. Mi ce that are homozygous (-/-) for deletion of the IL-6 gene were used t o investigate the role of this cytokine in MHV-68 infection. The resul ts showed that IL-6 is not essential for clearance of infectious MHV-6 8 from the lung or for the establishment, or control, of viral latency . Both IL-6 +/+ and -/- mice eliminated replicating virus from the res piratory tract within 15 days of infection, and their lungs remained c lear of infectious virus for greater than or equal to 150 days. Intere stingly, the IL-6 -/- mice had both increased numbers of natural kille r (NK)1.1+ cells and higher levels of NK cell activity than the +/+ co ntrols at 10-15 days after infection. However, there was no difference in the cytotoxic T cell activity between the two groups of mice. Leve ls of latent virus were comparable in IL-6 +/+ and -/- mice over the t ime course studied. Furthermore, analysis of the numbers, types, and a ctivation status of the various leukocyte subsets (other than NK cells ) in the bronchoalveolar lavage population, lymph nodes, and spleens o f +/+ and -/- mice revealed no striking differences. Apart from the ex pected lack of IL-6, cytokine profiles were not dramatically altered i n IL-6 -/- mice. Thus, there is no evidence for an obligatory role for IL-6 in T cell activation during infection with MHV-68. (C) 1998 Acad emic Press.