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Originally published In Press as doi:10.1074/jbc.M207079200 on August 20, 2002

J. Biol. Chem., Vol. 277, Issue 44, 42352-42357, November 1, 2002
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Purification of a Modified Form of Bovine Antithrombin III as an HIV-1 CD8+ T-cell Antiviral Factor*

Ralf Geiben-Lynn, Nancy Brown, Bruce D. Walker, and Andrew D. LusterDagger

From the Partners AIDS Research Center, Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129

CD8+ T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8+ T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8+ T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8+ T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.

* This research was funded in parts by grants from the Defense Advanced Research Projects Agency (MDA-972-97-1-00144), the Deutsche Forschungsgemeinschaft, and the National Institutes of Health (AI30914, AI28568, AI46999).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129. Tel.: 617-726-5710; Fax: 617-726-5651; E-mail: luster@helix.mgh.harvard.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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