Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor.
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.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology; D040081:Protein Array Analysis; D014779:Virus Replication; D023084:alpha-Defensins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D019742:Chemokines, CC; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3