In addition to their antibacterial activities, certain
antimicrobial peptides inactivate enveloped viruses, including the human immunodeficiency virus (HIV). To determine whether
peptide bactericidal activities are predictive of
antiviral activity, the anti-HIV properties of recombinant human
alpha-defensin 5, mouse
alpha-defensins, cryptdins (Crp) 3 and 4, and rhesus macaque myeloid
alpha-defensins (RMADs) 3 and 4 were determined in vitro. The
peptides, purified to homogeneity, had equivalent bactericidal activities that were similar to those of the native molecules. Nuclear magnetic resonance spectroscopy showed RMAD-4 and Crp3 had characteristic
alpha-defensin tridisulfide arrays. Of the
peptides analyzed, only RMAD-4 inhibited HIV infectivity at 150 microg/ml, and Crp3 unexpectedly increased HIV replication. Quantitative real-time PCRs for minus-strand
strong stop DNA and complete viral
cDNA synthesis were used to distinguish between preentry and postentry anti-HIV effects by RMAD-4. Viral exposure to RMAD-4 for 1 h prior to
infection reduced HIV minus-strand
strong stop DNA and HIV
cDNA by 4- to 20-fold during the first round of replication, showing that RMAD-4-exposed virions were not entering cells during the first 24 h. On the other hand, when RMAD-4 was added coincident with HIV inoculation, no anti-HIV activity was detected. Viral exposure to Crp3 resulted in a threefold increase in both HIV minus-strand
strong stop DNA and HIV
cDNA over the first round of replication. Therefore, two
alpha-defensins, RMAD-4 and Crp3, inhibit or augment HIV replication, respectively, by mechanisms that precede reverse transcription.