title: Human Alpha-Defensin HNP1 Increases HIV Traversal of the Epithelial Barrier: A Potential Role in STI-Mediated Enhancement of HIV Transmission.
abstract: Alpha-defensins, including human neutrophil peptides 1-3 (HNP1-3) and human defensin 5 (HD5), are elevated at the genital mucosa in individuals with sexually transmitted infections (STIs). The presence of STIs is associated with an increased risk of human immunodeficiency virus (HIV) transmission, suggesting there may be a role for defensins in early events of HIV transmission. HD5 has been demonstrated to contribute to STI-mediated increased HIV infectivity in vitro. HNPs exhibit anti-HIV activity in vitro. However, increased levels of HNPs have been associated with enhanced HIV acquisition and higher viral load in breast milk. This study found that HNP1, but not HD5, significantly disrupted epithelial integrity and promoted HIV traversal of epithelial barriers. Linear HNP1 with the same charges did not affect epithelial permeability, indicating that the observed effect of HNP1 on the epithelial barrier was structure dependent. These results suggest a role for HNP1 in STI-mediated enhancement of HIV transmission.
authors.affiliation: 1 Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.
authors.forename: Kimyata
authors.initials: K
authors.lastname: Valere
authors.affiliation: 2 Public Health Research Institute, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.
authors.forename: Aprille
authors.initials: A
authors.lastname: Rapista
authors.affiliation: 1 Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.|2 Public Health Research Institute, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Eugenin
authors.affiliation: 3 Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.affiliation: 1 Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.|2 Public Health Research Institute, Rutgers, The State University of New Jersey , New Jersey Medical School, Newark, New Jersey.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
mesh_terms: D004848:Epithelium / Q000276:immunology* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D054884:Host-Pathogen Interactions; D006801:Humans; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D023084:alpha-Defensins; C406413:human neutrophil peptide 1