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

Ivona Pandrea^2,*,, Thaidra Gaufin^*,, Jason M. Brenchley, Rajeev Gautam^*, Christopher Monjure^*, Aarti Gautam^*, Clint Coleman^*,, Andrew A. Lackner^*,, Ruy M. Ribeiro^||, Daniel C. Douek^¶ and Cristian Apetrei^*,#

^* Divisions of Comparative Pathology and Microbiology, Tulane National Primate Research Center, Covington, LA 70433; Department of Pathology and Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112; Immunopathogenesis Unit, Laboratory of Molecular Microbiology, and ^¶ Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ^|| Los Alamos National Laboratory, Los Alamos, NM 87545; and ^# Department of Tropical Medicine, School of Public Health, Tulane University, New Orleans, LA 70112

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases/National Center for Research Resources Grants R01 AI064066 and R21AI069935 (to I.P.), R01 AI065325 (to C.A.), and RR-00168 (to Tulane National Primate Research Center).

² Address correspondence and reprint requests to Dr. Ivona Pandrea, Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433. E-mail address: ipandrea{at}tulane.edu

³ Abbreviations used in this paper: Rh, rhesus macaque; AGM, African green monkey; sCD14, soluble CD14; SIVagm, African green monkey SIV; SIVmac, macaque SIV; Treg, T regulatory cell; VL, viral load.

⁴ The online version of this article contains supplemental material.