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1. Cutting Edge: Experimentally Induced Immune Activation in Natural Hosts of Simian Immunodeficiency Virus Induces Significant Increases in Viral Replication and CD4+ T Cell Depletion1

Author

Pandrea, Ivona, Gaufin, Thaidra, Brenchley, Jason M., Gautam, Rajeev, Monjure, Christopher, Gautam, Aarti, Coleman, Clint, Lackner, Andrew A., Ribeiro, Ruy M., Douek, Daniel C., and Apetrei, Cristian

Subjects
CD4-Positive T-Lymphocytes, Lipopolysaccharides, animal diseases, Recombinant Fusion Proteins, Simian Acquired Immunodeficiency Syndrome, Viral Load, Flow Cytometry, Lymphocyte Activation, Virus Replication, Article, Adjuvants, Immunologic, Chlorocebus aethiops, Chronic Disease, Animals, Interleukin-2, Diphtheria Toxin, Simian Immunodeficiency Virus
Abstract

Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable nonpathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and with stable viral loads for long periods of time. In vivo administration of LPS or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4(+) T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell proliferation are key factors in AIDS pathogenesis.

Published
2008

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