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首页> 外文期刊>AIDS Research and Human Retroviruses >Mutational Heterogeneity in p6 Gag Late Assembly (L) Domains in HIV-1 Subtype C Viruses from South Africa
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Mutational Heterogeneity in p6 Gag Late Assembly (L) Domains in HIV-1 Subtype C Viruses from South Africa

机译:来自南非的HIV-1亚型C病毒的p6 Gag后期装配(L)域中的突变异质性。

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摘要

Contradictory results have been reported on the impact of duplications/insertions in the HIV-1 gag-p6 late assembly domains [TSG101-binding P(T/S)APP motif and ALIX-binding LYPx(n)LxxL motif] heterogeneity following therapy failure. However, most studies are limited to small numbers of patients and do not include samples from South Africa, which has the largest number of HIV-1C-infected patients (HIV-1C(ZA)). In this study we compared the gag-p6 variability among HIV-1C(ZA)-infected patients from a South African clinical cohort who experienced antiretroviral therapy (ART) failure (n=845) with ART-naive HIV-1C(ZA) sequences (n=706) downloaded from the Los Alamos database. Partial (PTA/PTV/APP) or complete P(T/S)APP duplications were less frequent in HIV-1C(ZA) with ART failure compared to therapy-naive ones (14% vs. 30%; p<0.001). In contrast, the tetrapeptide PYxE insertion, recently described by us, occurred more frequently (5-fold) in therapy-failure patients (p<0.001) and was associated with a higher number of reverse transcriptase inhibitor (RTI) mutations (p=0.04) among patients failing ART.
机译:关于在治疗失败后HIV-1 gag-p6晚期组装域[TSG101结合P(T / S)APP基序和ALIX结合LYPx(n)LxxL基序]重复/插入影响的矛盾性结果报道矛盾。但是,大多数研究仅限于少数患者,并且不包括来自南非的样本,而南非的样本被HIV-1C感染的患者数量最多(HIV-1C(ZA))。在这项研究中,我们比较了来自南非临床队列的HIV-1C(ZA)感染患者的抗gag-p6变异性,这些患者经历过抗逆转录病毒治疗(ART)失败(n = 845)和未使用ART的HIV-1C(ZA)序列(n = 706)从Los Alamos数据库下载。与未经治疗的HIV-1C(ZA)相比,与未经治疗的HIV-1C(ZA)相比,部分(PTA / PTV / APP)或完全P(T / S)APP复制的频率较低(14%比30%; p <0.001)。相反,我们最近描述的四肽PYxE插入在治疗失败的患者中更频繁地发生(5倍)(p <0.001),并且与更高数量的逆转录酶抑制剂(RTI)突变相关(p = 0.04) )在ART失败的患者中。

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