8,12,13 There are six alpha defensins: human neutrophil peptide (HNP)1–4 and human defensin (HD) 5 and 6. HNPs 1–3 share a high degree of homology with only the

amino terminal amino acid differing between them. Alpha defensins are synthesized as pre-prodefensins that are cleaved by proteases Selleck Selumetinib to create an active peptide which displays antibacterial activity against Gram-positive and Gram-negative bacteria, fungi, and yeast; and antiviral effects against HIV-1, HSV-1, and HSV-2.12 Intriguingly, however, HD5 and HD6 enhance HIV replication by themselves as well as in the presence of gonorrheal infection.20 However, the exact mechanism of infection remains to be determined. Beta defensins HBD1–6 are structurally similar to alpha defensins and have broad inhibitory activity against a range of pathogens including HIV-1.12 Genome scans have revealed at least 28 putative human beta defensins; though, only six have been discovered, of which four are present in the FRT.8,12,13 HBD1–3 have direct and indirect anti-HIV-1 activity.21,22 Similar to other antimicrobials, they interact directly with the viral envelope.12,21 Furthermore, find more they act upon target cell populations to decrease levels of the HIV-1 CXCR4 co-receptor as well as inhibit

the early steps of viral replication.21–23 Cathelicidins are a family of cationic antimicrobial peptides of which only one is found in humans, cathelicidin (hCAP-18/LL-37).24 LL-37 is present in the FRT and is composed of three domains: a signal peptide region, an N-terminal cathelin-like domain, and a C-terminal antimicrobial domain.9,24 The mature

peptide LL-37 is generated from hCAP-18 by protease cleavage, is broadly antibacterial, and inhibits HIV-1 replication Dimethyl sulfoxide in vitro independently of changes in HIV-1 co-receptor expression. Intriguingly, the cathelin-domain also has antibacterial activity but no disclosed anti-HIV-1 activity.5,25 Uniquely, hCAP-18 is cleaved to form ALL-38 by gastricsin, a protease present in seminal fluid that is reaction dependent on low pH found in the vagina.26 ALL-38 has a similar antibacterial profile to LL-37, but its anti-HIV activity is unknown. This remarkable mechanism for antimicrobial activation highlights the importance of male sexual fluids in modulating the protective response in the FRT.9,13 Secretory leukocyte protease inhibitor and Elafin, located together on chromosome 20, are members of whey acidic protein (WAP) family that possess a conserved whey four disulfide core domain (WFDC).27,28 The pair are endogenous protease inhibitors involved in the control of inflammatory responses and tissue remodeling.27,28 Unlike SLPI, Elafin is relatively restricted in its target population acting mainly on neutrophil and pancreatic elastase and neutrophil proteinase 3. Both proteins also demonstrate anti-HIV-1 activity that is independent of their protease inhibitor function.