HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef
HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef
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DOI：
10.1186/1742-4690-8-103
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发表时间：
2011-12-15
期刊：
影响因子：
3.3
通讯作者：
Gupta, Ravindra K.
中科院分区：
文献类型：
--
作者：
Sauter, Daniel;Hue, Stephane;Gupta, Ravindra K.
背景：一种新的HIV-1亚型，被称为P组，最近在两名喀麦隆裔无血缘关系的患者中被发现。HIV-1 P组在系统发育上与SIVgor聚集，这表明它是大猩猩跨物种传播的结果。直到今天，HIV-1 P组仅在两名患者中检测到，其对人类宿主的适应程度在很大程度上是未知的。先前的数据表明，大流行的HIV-1 M组病毒，而非大流行的O组病毒或罕见的N组病毒，可以有效地拮抗限制因子tetherin的人类同源物（BST-2, HM1.24, CD317），这表明灵长类慢病毒可能必须获得抗tetherin活性才能在人群中有效传播。到目前为止，已知三种SIV/ HIV基因产物（vpu、nef和env）通常以物种特异性的方式具有抵消灵长类动物tetherin蛋白的潜力。在这里，我们研究了P群可能在人类中传播了多长时间，并确定了其对抗人类绳朊的能力，作为适应人类的指标。结果：我们的数据表明HIV-1 P组在1845年至1989年间进入人群。来自P组病毒的Vpu、Env和Nef蛋白都不能中和人类或大猩猩的tetherin以促进HIV-1病毒粒子的有效释放，尽管P组的Nef蛋白都能从细胞表面适度下调大猩猩的tetherin。值得注意的是，来自两种hiv - 1p毒株的Vpu、Env和Nef等位基因都能够降低CD4细胞表面的表达。结论：我们对两种报告的HIV-1 P组病毒的分析表明，人畜共患病发生在过去的170年里，进一步支持了大流行的HIV-1 M组毒株比非大流行或罕见的O、N和P组病毒更能适应人类。HIV-1 P组在人群中的有限传播可能是由于无法拮抗人栓蛋白。
Background: A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a crossspecies transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain antitetherin activity for efficient spread in the human population. Thus far, three SIV/ HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.Results: Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.Conclusions: Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than nonpandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population.