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Originally published In Press as doi:10.1074/jbc.M209964200 on November 5, 2002

J. Biol. Chem., Vol. 278, Issue 3, 1569-1574, January 17, 2003
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HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family*

Ralf Geiben-LynnDagger §, Mischo KursarDagger , Nancy V. BrownDagger , Marylyn M. AddoDagger , Hungyi Shau, Judy Lieberman||, Andrew D. Luster**, and Bruce D. WalkerDagger

From the Dagger  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,  Division of Surgical Oncology, UCLA School of Medicine, Los Angeles, California 90095-1782, and || Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115

CD8+ T-cells are a major source for the production of non-cytolytic factors that inhibit HIV-1 replication. In order to characterize further these factors, we analyzed gene expression profiles of activated CD8+ T-cells using a human cDNA expression array containing 588 human cDNAs. mRNA for the chemokine I-309 (CCL1), the cytokines granulocyte-macrophage colony-stimulating factor and interleukin-13, and natural killer cell enhancing factors (NKEF) -A and -B were up-regulated in bulk CD8+ T-cells from HIV-1 seropositive individuals compared with seronegative individuals. Recombinant NKEF-A and NKEF-B inhibited HIV-1 replication when exogenously added to acutely infected T-cells at an ID50 (dose inhibiting HIV-1 replication by 50%) of ~130 nM (3 µg/ml). Additionally, inhibition against dual-tropic simian immunodeficiency virus and dual-tropic simian-human immunodeficiency virus was found. T-cells transfected with NKEF-A or NKEF-B cDNA were able to inhibit 80-98% HIV-1 replication in vitro. Elevated plasma levels of both NKEF-A and NKEF-B proteins were detected in 23% of HIV-infected non-treated individuals but not in persons treated with highly active antiviral therapy or uninfected persons. These results indicate that the peroxiredoxin family members NKEF-A and NKEF-B are up-regulated in activated CD8+ T-cells in HIV infection, and suggest that these antioxidant proteins contribute to the antiviral activity of CD8+ T-cells.

* This work was supported in part by Grant MDA-972-97-1-00144 from the Defense Advanced Research Projects Agency, the Deutsche Forschungsgemeinschaft, and Grants AI30914, AI28568, and AI46999 from the National Institutes of Health.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.

§ To whom correspondence should be addressed: Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129. Tel.: 617-924-8918; Fax: 617-924-0302; E-mail: acceleration@rcn.com.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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