Zapata Wildeman, Aguilar-Jiménez Wbeimar, Feng Zhimin, Weinberg Aaron, Russo Aniello, Potenza Nicoletta, Estrada Hernando, Rugeles María T
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Colombia.
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
Microbes Infect. 2016 Mar;18(3):211-9. doi: 10.1016/j.micinf.2015.10.009. Epub 2015 Nov 6.
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.
防御素、核糖核酸酶和细胞因子存在于黏膜屏障处，即HIV进入人体的主要部位，并且可能是HIV-1暴露血清阴性个体（HESN）在性接触期间所表现出的抗性表型的潜在介质。我们旨在确定可溶性因子在对HIV-1感染的天然抗性中的作用。从60名HESN、60名血清阳性（SP）个体和61名健康对照（HC）中采集阴道/宫颈/口腔黏膜样本。通过qPCR对人中性粒细胞肽1（hNP-1）、人β防御素（hBD）2和3、核糖核酸酶、MIP-1β和RANTES的mRNA转录本进行定量，并使用基于重组的体外单轮病毒感染性测定法来评估hBD和核糖核酸酶的抗HIV-1活性。与HC相比，HESN口腔黏膜中hNP-1、hBD的mRNA表达水平显著更高（P<0.05）。在生殖器黏膜中，与HC相比，HESN中MIP-1β、RANTES和核糖核酸酶的mRNA水平显著更高（P<0.05）。hBD和核糖核酸酶可抑制HIV-1复制，尤其是在病毒生命周期的进入、逆转录和核输入阶段的R5毒株。hNP-1、hBD、MIP-1β、RANTES和核糖核酸酶共同作用，可能有助于在性接触期间抵抗HIV-1。此外，hBD和核糖核酸酶在体外对HIV-感染的抑制作用表明，它们可能被开发为潜在的抗逆转录病毒药物。
