Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1

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 solublefactors 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-1b 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-1b, 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-1b, 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.

• Autores: Aguilar Jiménez, Wbeimar; Feng, Zhimin; Russo, Aniello; Potenza, Nicoletta; Estrada, Hernando; Rugeles López, María Teresa; Weinberg, Aaron
• Tipo de recurso: Article of journal
• Fecha de publicación: 2016
• Institución: Universidad Cooperativa de Colombia
• Repositorio: Repositorio UCC
• OAI Identifier: oai:repository.ucc.edu.co:20.500.12494/1352
• Acceso en línea: https://hdl.handle.net/20.500.12494/1352
• Palabra clave: Antiviral; HIV-1; (Human immunodeficiency virus type 1); RNases; Natural resistance; Exposed seronegative; individuals; HBDs
• Rights: embargoedAccess
• License: Licencia CC