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• W2164081767 abstract "Despite the clinical importance of virus-induced immunosuppression, how virus infection may lead to a generalized suppression of the host immune response is poorly understood. To elucidate the principles involved, we analyzed the mechanism by which a lymphocytic choriomeningitis virus (LCMV) variant produces a generalized immune suppression in its natural host, the mouse. Whereas adult mice inoculated intravenously with LCMV Armstrong rapidly clear the infection and remain immunocompetent, inoculation with the Armstrong-derived LCMV variant clone 13, which differs from its parent virus at only two amino acid positions, by contrast results in persistent infection and a generalized deficit in responsiveness to subsequent immune challenge. Here we show that the immune suppression induced by LCMV clone 13 is associated with a CD8-dependent loss of interdigitating dendritic cells from periarteriolar lymphoid sheaths in the spleen and, functionally, with a deficit in the ability of splenocytes from infected mice to stimulate the proliferation of naive T cells in a primary mixed lymphocyte reaction. Dendritic cells are not depleted in immunocompetent Armstrong-infected mice. LCMV Armstrong and clone 13 exhibit differences in their tropism within the spleen, with clone 13 causing a higher level of infection of antigen-presenting cells in the white pulp, including periarterial interdigitating dendritic cells, than Armstrong, thereby rendering these cells targets for destruction by the antiviral CD8+ cytotoxic T-lymphocyte response which is induced at early times following infection with either virus. Our findings illustrate the key role that virus tropism may play in determining pathogenicity and, further, document a mechanism for virus-induced immunosuppression which may contribute to the clinically important immune suppression associated with many virus infections, including human immunodeficiency virus type 1." @default.
• W2164081767 created "2016-06-24" @default.
• W2164081767 creator A5001380638 @default.
• W2164081767 creator A5010023851 @default.
• W2164081767 creator A5085628631 @default.
• W2164081767 date "1995-02-01" @default.
• W2164081767 modified "2023-10-18" @default.
• W2164081767 title "Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression" @default.
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• W2164081767 doi "https://doi.org/10.1128/jvi.69.2.1059-1070.1995" @default.
• W2164081767 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/188677" @default.
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