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 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-1ß 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-1ß, 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-1ß, 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. © 2015 Institut Pasteur.

• Autores: Zapata Builes, Wildeman; Aguilar-Jiménez W.; Feng Z.; Weinberg A.; Russo A.; Potenza N.; Estrada H.; Rugeles M.T.
• 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:20.500.12494/41505
• Acceso en línea: https://doi.org/10.1016/j.vetmic.2016.12.039; https://hdl.handle.net/20.500.12494/41505
• Palabra clave: angiogenin; beta defensin 2; beta defensin 3; macrophage inflammatory protein 1beta; maraviroc; messenger RNA; n [4 [[[6,7 dihydro 2 (4 methylphenyl) 5h benzocyclohepten 8 yl]carbonyl]amino]benzyl] n,n dimethyl 2h tetrahydropyran 4 aminium chloride; neutrophil peptide 1; plerixafor; protein; RANTES; ribonuclease; unclassified drug; zidovudine; immunologic factor; adult; antiviral activity; Article; CD4+ T lymphocyte; controlled study; dose response; human; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; in vitro study; in vivo study; innate immunity; life cycle; major clinical study; mouth mucosa; polymerase chain reaction; priority journal; protein analysis; protein expression; protein function; quantitative analysis; reverse transcription; sexual intercourse; uterine cervix mucosa; vagina mucosa; viral tropism; virus entry; virus infectivity; virus inhibition; virus load; virus replication; virus resistance; virus strain; adolescent; disease resistance; fema
• Rights: closedAccess
• License: http://purl.org/coar/access_right/c_14cb