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https://www.arca.fiocruz.br/handle/icict/6755
LETHAL ENCEPHALITIS IN MYELOID DIFFERENTIATION FACTOR 88-DEFICIENT MICE INFECTED WITH HERPES SIMPLEX VIRUS 1
Author
Affilliation
Universidade Federal de Minas Gerais. Departamento de Microbiologia. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Microbiologia. Belo Horizonte, MG, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Disease. The Laboratory of Viral Diseases. Bethesda, MA, USA.
Universidade Federal de Minas Gerais. Departamento de Patologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Osaka University. Research Institute for Microbial Diseases. The Department of Host Defense. Osaka, Japan.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Microbiologia. Belo Horizonte, MG, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Disease. The Laboratory of Viral Diseases. Bethesda, MA, USA.
Universidade Federal de Minas Gerais. Departamento de Patologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Osaka University. Research Institute for Microbial Diseases. The Department of Host Defense. Osaka, Japan.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.
Abstract
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.
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