The role of CD40 in LP-BM5 infection of mixed glial cells (VIR1P.1158)

Abstract

Abstract LP-BM5 retrovirus infection is an established murine model of HIV infection in humans due to that susceptible strains of mice (such as B6) develop immunodeficiency syndrome. Previously, we have shown that infected B6 mice developed peripheral neuropathy and CD40 knockout (KO) mice displayed less mechanical hypersensitivity (behavioral sign of peripheral neuropathy) post-LP-BM5 infection. The spinal cord viral RNA levels were significantly lower in CD40 KO mice compared to wild type (WT) B6 mice, which is correlated with decreased lumbar spinal cord cytokines, IL-1-beta, IL-6 and IFN-gamma. It is known that LP-BM5 can infect glial cells directly. We hypothesized that glial cells in CD40 KO mice were less susceptible to LP-BM5 infection. To test this hypothesis, primary spinal cord mixed glial cells from both WT and CD40 KO mice were infected with various doses of LP-BM5. Consistent with our in vivo findings, levels of viral RNA are significantly lower in mixed glial cells from CD40 KO mice than that from WT mice. Further, levels of cytokines, IL-1-beta, IL-6, TNF-alpha, IFN-gamma, and IL-12p40 were measured in the supernatants. LP-BM5 only induced minimal increase of these cytokines and there no significant differences between WT and CD40 KO mice were observed. Our data indicate that glial cells lacking CD40 are more resistant to LP-BM5 infection and this resistance does not seem to be due to the decreased production of proinflammatory cytokines by glial cells.