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Originally published in Science Express on 26 September 2002
Science 1 November 2002:
Vol. 298. no. 5595, pp. 995 - 1000
DOI: 10.1126/science.1076185
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Research Articles

Contribution of Human alpha -Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor

Linqi Zhang,1* Wenjie Yu,1 Tian He,1 Jian Yu,1 Rebecca E. Caffrey,2 Enrique A. Dalmasso,2 Siyu Fu,2 Thang Pham,2 Jianfeng Mei,2 Jaclyn J. Ho,1 Wenyong Zhang,1 Peter Lopez,1 David D. Ho1*

It has been known since 1986 that CD8 T lymphocytes from certain HIV-1-infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as alpha -defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human alpha -defensins. Synthetic and purified preparations of alpha -defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that alpha -defensin 1, 2, and 3 collectively account for much of the anti-HIV-1 activity of CAF that is not attributable to beta -chemokines.

1 Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
2 Ciphergen Biosystems, Inc., 6611 Dumbarton Circle, Fremont, CA 94555, USA.
*   To whom correspondence should be addressed. E-mail: lzhang{at}adarc.org (L.Z.); dho{at}adarc.org (D.D.H.)

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W. Wang, A. M. Cole, T. Hong, A. J. Waring, and R. I. Lehrer (2003)
J. Immunol. 170, 4708-4716
   Abstract »    Full Text »    PDF »
The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors.
C. E. Mackewicz, C. S. Craik, and J. A. Levy (2003)
PNAS 100, 3433-3438
   Abstract »    Full Text »    PDF »
Mechanisms of Antimicrobial Peptide Action and Resistance.
M. R. Yeaman and N. Y. Yount (2003)
Pharmacol. Rev. 55, 27-55
   Abstract »    Full Text »    PDF »
NP-1, a Rabbit {alpha}-Defensin, Prevents the Entry and Intercellular Spread of Herpes Simplex Virus Type 2.
S. Sinha, N. Cheshenko, R. I. Lehrer, and B. C. Herold (2003)
Antimicrob. Agents Chemother. 47, 494-500
   Abstract »    Full Text »    PDF »
HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family.
R. Geiben-Lynn, M. Kursar, N. V. Brown, M. M. Addo, H. Shau, J. Lieberman, A. D. Luster, and B. D. Walker (2003)
J. Biol. Chem. 278, 1569-1574
   Abstract »    Full Text »    PDF »
Cutting Edge: L-Selectin (CD62L) Expression Distinguishes Small Resting Memory CD4+ T Cells That Preferentially Respond to Recall Antigen.
R. L. Hengel, V. Thaker, M. V. Pavlick, J. A. Metcalf, G. Dennis Jr., J. Yang, R. A. Lempicki, I. Sereti, and H. C. Lane (2003)
J. Immunol. 170, 28-32
   Abstract »    Full Text »    PDF »
Mono-ADP-Ribosylation: A Tool for Modulating Immune Response and Cell Signaling.
D. Corda and M. Di Girolamo (2002)
Sci. STKE 2002, pe53
   Abstract »    Full Text »    PDF »
Mysterious CD8 Antiviral Factor Unmasked.
(2002)
Journal Watch Infectious Diseases 2002, 5
   Full Text »
CD8 Antiviral Factor identified.
(2002)
AIDS Clinical Care 2002, 12
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