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

Science, 1 November 2002
Vol. 298, Issue 5595, p. 995-1000
DOI: 10.1126/science.1076185

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

  1. Linqi Zhang1,*,
  2. Wenjie Yu1,
  3. Tian He1,
  4. Jian Yu1,
  5. Rebecca E. Caffrey2,
  6. Enrique A. Dalmasso2,
  7. Siyu Fu2,
  8. Thang Pham2,
  9. Jianfeng Mei2,
  10. Jaclyn J. Ho1,
  11. Wenyong Zhang1,
  12. Peter Lopez1,
  13. David D. Ho1,*
  1. 1 Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
  2. 2 Ciphergen Biosystems, Inc., 6611 Dumbarton Circle, Fremont, CA 94555, USA.


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 α-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 α-defensins. Synthetic and purified preparations of α-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that α-defensin 1, 2, and 3 collectively account for much of the anti–HIV-1 activity of CAF that is not attributable to β-chemokines.

  • * To whom correspondence should be addressed. E-mail: lzhang{at} (L.Z.); dho{at} (D.D.H.)

  • Received for publication 16 July 2002.
  • Accepted for publication 17 September 2002.


L. Zhang, W. Yu, T. He, J. Yu, R. E. Caffrey, E. A. Dalmasso, S. Fu, T. Pham, J. Mei, J. J. Ho, W. Zhang, P. Lopez, and D. D. Ho, Contribution of Human α-Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor. Science 298, 995-1000 (2002).

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S. N. Asin, D. Wildt-Perinic, S. I. Mason, A. L. Howell, C. R. Wira, and M. W. Fanger
The Journal of Infectious Disease 187, 1522-1533 (15 May 2003)

The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors
J. Stebbing, B. Gazzard, L. Kim, S. Portsmouth, A. Wildfire, I. Teo, M. Nelson, M. Bower, F. Gotch, S. Shaunak et al.
Blood 101, 4000-4004 (15 May 2003)

Retrocyclin, an Antiretroviral {theta}-Defensin, Is a Lectin
W. Wang, A. M. Cole, T. Hong, A. J. Waring, and R. I. Lehrer
J. Immunol. 170, 4708-4716 (1 May 2003)

Innate Immunity in Human Immunodeficiency Virus Infection: Effect of Viremia on Natural Killer Cell Function
S. Kottilil, T.-W. Chun, S. Moir, S. Liu, M. McLaughlin, C. W. Hallahan, F. Maldarelli, L. Corey, and A. S. Fauci
The Journal of Infectious Disease 187, 1038-1045 (1 April 2003)

The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors
C. E. Mackewicz, C. S. Craik, and J. A. Levy
Proc. Natl. Acad. Sci. USA 100, 3433-3438 (18 March 2003)

Mechanisms of Antimicrobial Peptide Action and Resistance
M. R. Yeaman, and N. Y. Yount
Pharmacol. Rev. 55, 27-55 (1 March 2003)

Nicotinamide: An Oral Antimicrobial Agent with Activity against Both Mycobacterium tuberculosis and Human Immunodeficiency Virus
M. F. Murray, and N. Y. Yount
Clinical Infectious Diseases 36, 453-460 (15 February 2003)

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
Antimicrob. Agents Chemother. 47, 494-500 (1 February 2003)

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
J Biol Chem 278, 1569-1574 (17 January 2003)

Nonlinear Dose-Response Relationship in the Immune System following Exposure to Ionizing Radiation: Mechanisms and Implications
S.-Z. Liu, M. Kursar, N. V. Brown, M. M. Addo, H. Shau, J. Lieberman, A. D. Luster, and B. D. Walker
Dose-Response 1, 15401420390844483-15401420390844483 (1 January 2003)

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, J. Yang, R. A. Lempicki, I. Sereti, and H. C. Lane
J. Immunol. 170, 28-32 (1 January 2003)

Mono-ADP-Ribosylation: A Tool for Modulating Immune Response and Cell Signaling
D. Corda, and M. Di Girolamo
Sci Signal 2002, pe53-pe53 (17 December 2002)

Mysterious CD8 Antiviral Factor Unmasked
M. Di Girolamo
JWatch Infect. Diseases 2002, 5-5 (21 November 2002)

CD8 Antiviral Factor identified
M. Di Girolamo
AIDS Clin Care 2002, 12-12 (1 November 2002)

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