Murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity

作者：Larson Jennifer D; Thurman Joshua M; Rubtsov Anatoly V; Claypool David; Marrack Philippa^*; van Dyk Linda F; Torres Raul M; Pelanda Roberta

来源：Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(18): E1092-E1100.

DOI：10.1073/pnas.1203019109

• antibody
• mouse gammaherpesvirus

Gammaherpesvirus infections, such as those caused by EBV, have been suggested to promote the development of autoimmunity. To test this idea, we infected healthy WT and lupus-prone B6. Sle123 mice with an EBV-related and rodent-specific gammaherpesvirus,.HV68. Although acute gamma HV68 infection increased autoantibody levels for 4 to 6 wk, latent infection inhibited these responses for 1 y. The inhibition of autoantibody expression was only observed in B6.Sle123 females and not in males, which already displayed lower autoantibody titers. Contrary to the initial hypothesis, infection of young B6.Sle123 mice, both male and female, resulted in suppression of lymphoid activation and expansion and of glomerular inflammation and sclerosis, preserving kidney function. Moreover, gamma HV68 infection led to reduced autoantibody titers, lymphoid activation, and glomerular inflammation whether lupus-prone females were infected before or during disease manifestation. Finally,.HV68 infection also inhibited autoantibody production in the genetically distinct MRL/lpr lupus-prone mice. Our findings indicate that gamma HV68 infection strongly inhibits the development and progression of lupus-like disease in mice that spontaneously develop this condition mediating its beneficial effects at the humoral, cellular, and organ levels. The mechanisms by which the virus exerts this down-modulatory action are not yet clear, but appear to operate via reduced activation of dendritic cells, T cells, and B cells. Gammaherpesviruses coevolved with the vertebrate immune systems, establishing lifelong infections in humans and other mammals. Our findings that gamma HV68 infection prevents rather than exacerbates autoimmunity in mice suggest that infection with gammaherpesviruses may be protective rather than pathological in most individuals.

• 出版日期2012-5-1