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The Journal of Immunology, 2004, 173: 515-520.
Copyright © 2004 by The American Association of Immunologists

Activity of {alpha}- and {theta}-Defensins against Primary Isolates of HIV-11

Wei Wang2,*, Sherry M. Owen2,{dagger}, Donna L. Rudolph{dagger}, Alexander M. Cole*, Teresa Hong*, Alan J. Waring*, Renu B. Lal{dagger} and Robert I. Lehrer3,*

* Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095; and {dagger} HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333

{theta}-Defensins are lectin-like, cyclic octadecapeptides found in the leukocytes of nonhuman primates. They are also homologues of the more familiar {alpha}-defensins expressed by humans and certain other mammals. This study compares the ability of six {theta}-defensins (hominid retrocyclins 1–3 and rhesus {theta}-defensins 1–3) and four human {alpha}-defensins (human neutrophil peptides (HNPs) 1–4) to bind gp120 and CD4. In addition, we compared the ability of these {theta}-defensins and HNP-1 to protect J53-BL cells (an indicator cell line) from primary HIV-1 isolates that varied in subtype and coreceptor usage. The most potent {theta}-defensin, retrocyclin-2, bound with exceptionally high affinity to gp120 (KD, 9.4 nM) and CD4 (KD, 6.87 nM), and its effectiveness against subtype B isolates (IC50, 1.05 ± 0.28 µg/ml; 520 ± 139 nM) was approximately twice as great as that of HNP-1 on a molar basis. We also show, for the first time, that human {alpha}-defensins, HNPs 1–3, are lectins that bind with relatively high affinity to gp120 (KD range, 15.8–52.8 nM) and CD4 (KD range, 8.0–34.9 nM). Proteins found in human and FBS bound exogenous HNP-2 and retrocyclin-1, and competed with their ability to bind gp120. However, even the low concentrations of {alpha}-defensins found in normal human serum suffice to bind over half of the gp120 spikes on HIV-1 and a higher percentage of cell surface CD4 molecules. Although this report principally concerns the relationship between carbohydrate-binding and the antiviral properties of {alpha}- and {theta}-defensins, the lectin-like behavior of defensins may contribute to many other activities of these multifunctional peptides.


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