Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis

PLoS Pathogens

Costanza Casiraghi¹  Sehyun Cho¹  Iryna Shanina¹  Marc S. Horwitz¹  Marcia A. Blackman²  Michael L. Freeman² 

[1] Department of Microbiology and Immunology, The University of British Columbia, Vancouver, British Columbia, Canada;Trudeau Institute, Saranac Lake, New York, United States of America

关键词: T cells;    Central nervous system;    Multiple sclerosis;    Cytotoxic T cells;    Spinal cord;    Mouse models;    Cloning;    Cytokines;   

DOI  :  10.1371/journal.ppat.1002715

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.

【 授权许可】

CC BY