| First Author | Mansur DS | Year | 2005 |
| Journal | Am J Pathol | Volume | 166 |
| Issue | 5 | Pages | 1419-26 |
| PubMed ID | 15855642 | Mgi Jnum | J:98429 |
| Mgi Id | MGI:3578467 | Doi | 10.1016/S0002-9440(10)62359-0 |
| Citation | Mansur DS, et al. (2005) Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1. Am J Pathol 166(5):1419-26 |
| abstractText | Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88(-/-) mice, but not macrophages from TRL2(-/-) or from wild-type mice, were unable to produce tumor necrosis factor-alpha in response to HSV-1 exposure. Additionally, although TLR2(-/-) mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88(-/-) mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs. |
