TY - JOUR T1 - Role of Dendritic Cells in Differential Susceptibility to Viral Demyelinating Disease A1 - Hou, Wanqiu A1 - So, Eui Young A1 - Kim, Byung S Y1 - 2007/08/24 N2 -
Many chronic viral diseases are associated with prolonged viral persistence levels, which vary from one individual to another. However, the mechanisms of differential susceptibility to persistent viral infections are unknown. Theiler murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease similar to multiple sclerosis. In this study, we investigated the potential mechanisms of differential susceptibility to chronic viral persistence in the central nervous system following infection with TMEV. Our results indicate that differential interactions between virus and dendritic cells (DCs), leading to the induction of anti-viral immunity, are critical in determining resistance or susceptibility to virus-induced chronic demyelinating disease. DCs from susceptible mice are much more permissive to viral infection, resulting in severe deficiencies in their development, expansion, and function, whereas DCs from resistant mice are not permissive. Consequently, the DCs in susceptible mice are responsible for poor anti-viral T cell activation, permitting viral persistence and disease development in the host. Interestingly, the administration of additional DCs or pre-activated virus-resistant DCs enables susceptible mice to resist persistent viral infection and disease development. This knowledge may be useful in devising effective means to induce strong anti-viral immune responses, thereby protecting the host from virus-associated chronic diseases caused by persistent viral infection.