title: Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1.
abstract: Defensins, RNases and cytokines are present at mucosal barriers, main ports of HIV entry, and are potential mediators of the resistant phenotype exhibited by HIV-1-exposed seronegative individuals (HESN) during sexual exposure. We aimed to determine the role of soluble factors in natural resistance to HIV-1 infection. Vaginal/endocervical/oral mucosal samples were taken from 60 HESN, 60 seropositive (SP) and 61 healthy controls (HC). Human neutrophil peptide 1 (hNP-1), human beta defensin (hBD) 2 and 3, RNases, MIP-1β and RANTES mRNA transcripts were quantified by qPCR and in vitro single-round, recombinant-based viral infectivity assay was used to evaluate the anti-HIV-1 activity of hBDs and RNases. HESN expressed significantly higher levels of hNP-1, hBDs mRNA in oral mucosa compared to HC (P < 0.05). In genital mucosa, significantly higher mRNA levels of MIP-1β, RANTES and RNases were found in HESN compared to HC (P < 0.05). HBDs and RNases inhibit HIV-1 replication, particularly R5 at entry, reverse transcription and nuclear import of the viral life cycle. hNP-1, hBDs, MIP-1β, RANTES and RNases, collectively could contribute to HIV-1 resistance during sexual exposure. Moreover, the inhibition of HIV-1 infection in vitro by hBDs and RNases suggests that they may be exploited as potential antiretrovirals.
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Colombia.
authors.forename: Wildeman
authors.initials: W
authors.lastname: Zapata
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
authors.forename: Wbeimar
authors.initials: W
authors.lastname: Aguilar-Jiménez
authors.affiliation: Department of Biological Sciences, Case Western Reserve University, School of Dental Medicine, Cleveland, OH, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Biological Sciences, Case Western Reserve University, School of Dental Medicine, Cleveland, OH, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Department of Life Sciences, Second University of Naples, Italy.
authors.forename: Aniello
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Life Sciences, Second University of Naples, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Potenza
authors.affiliation: HERES Salud, IPS, Santa Marta, Colombia.
authors.forename: Hernando
authors.initials: H
authors.lastname: Estrada
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia. Electronic address: maria.rugeles@udea.edu.co.
authors.forename: María T
authors.initials: MT
authors.lastname: Rugeles
mesh_terms: D000293:Adolescent; D000328:Adult; D060467:Disease Resistance; D005260:Female; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007155:Immunologic Factors / Q000032:analysis* / Q000235:genetics; D008297:Male; D055815:Young Adult
chemical_list: D007155:Immunologic Factors
keywords: Antiviral; HBDs; HIV-1 (Human immunodeficiency virus type 1); HIV-1 exposed seronegative individuals; Natural resistance; RNases