α-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors

Background: CD8 T cells from healthy HIV-infected individuals inhibit HIV replication in infected CD4 T cells by a non-cytotoxic mechanism mediated by a soluble CD8 cell antiviral factor, CAF Recently, the antimicrobial peptides, alpha-defensins, were reported to constitute CAF. Objective: To examine the antiviral activity of a-defensins and address their potential role in CD8 cell non-cytotoxic antiviral responses. Design and methods: A purified mixture of human neutrophil proteins (HNP) 1-3 (alpha-defensins) was used to examine the effect of alpha-defensins on HIV virions and on HIV replication in CD4 cells treated prior to or post infection. alpha-Defensin expression was analyzed at the RNA and protein level in CD8 cells as well as in various other cell types. Antibodies to the defensins were tested for their ability to inhibit CAF activity in CD8 cell culture fluids. Results: The alpha-defensins exhibited anti-HIV activity on at least two levels: directly inactivating virus particles; and affecting the ability of target CD4 cells to replicate the virus. However, while we could demonstrate alpha-defensins in neutrophils and monocytes, we found no evidence for the production of these pepticles by CD8 T cells. No messenger RNA encoding these proteins was detected in purified CD8 T cells, nor did these cells produce intracellular or extracellular a.-defensin peptides. Moreover, antibodies specific for human alpha-defensins 1, 2, and 3 did not block the antiviral activity of CAF-active CD8 cell culture fluids. Conclusions: The alpha-defensins are not produced by CD8 cells but unexpectedly were found to be expressed in monocytes. alpha-Defensins can have anti-HIV activity but are not CD8 cell antiviral factors. (C) 2003 Lippincott Williams Wilkins.