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Published online September 26, 2002
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Zhang, L. || Ho, D. D.

Submitted on July 16, 2002
Accepted on September 17, 2002

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. Ho 1*

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: dho@adarc.org.

It is 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 non-progressors with HIV-1 infection were stimulated. These proteins were identified as {alpha}-defensins-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}-defensins-1, -2, and -3 collectively account for the anti-HIV-1 activity of CAF that is not attributable to ß-chemokines.

Science 10.1126/science.1076185
Copyright © 2002 by The American Association for the Advancement of Science. All rights reserved.

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