Lack of adaptation to human tetherin in HIV-1 group O and P.
Lack of adaptation to human tetherin in HIV-1 group O and P.
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DOI：
10.1186/1742-4690-8-78
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发表时间：
2011-09-28
期刊：
影响因子：
3.3
通讯作者：
Cannon PM
中科院分区：
文献类型：
--
作者：
Yang SJ;Lopez LA;Exline CM;Haworth KG;Cannon PM
HIV-1 病毒分为四个不同的组：M、N、O 和 P。尽管基因组结构相同，但只有 M 组病毒才导致艾滋病在全球范围内的流行，这表明它们对人类宿主具有更好的适应能力。此前有报道称M组Vpu蛋白能够下调CD4并抵消BST-2/tetherin限制，而O组Vpu蛋白不能拮抗tetherin。这促使我们研究 O 组病毒和相关的 P 组病毒在 Vpu 或另一种病毒蛋白中是否具有功能性抗系链蛋白活性，并进一步绘制 M 组 Vpu 对抗人类系链蛋白所需的残基图谱。我们发现 O 组和 P 组病毒的 Vpu 和 Nef 蛋白缺乏针对人类系链蛋白的活性。此外，我们在完全感染性的 O 型原病毒克隆中没有发现抗人类系链蛋白活性的证据，排除了该病毒中存在替代抗系链蛋白因子的可能性。有趣的是，O 组病毒和 P 组病毒的 Nef 蛋白都保留了针对灵长类动物系链蛋白的活性。通过在功能组 M 和非功能组 O Vpu 蛋白之间制作嵌合体，我们能够绘制出 M 组 Vpu 的前 18 个氨基酸，这些氨基酸在该蛋白拮抗人系链蛋白的能力中发挥着重要作用。我们进一步证明了残基丙氨酸18对于M组Vpu活性的重要性。该残基位于蛋白质 TM 结构域中保守丙氨酸的对角线上，对于特定的 Vpu-tetherin 相互作用是必需的。 HIV-1 O 组和 P 组中缺乏人类特异性抗系链蛋白活性，表明这些病毒无法适应人类宿主，这可能限制了它们的传播。
HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.
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影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
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3.3
作者：
Hauser H;Lopez LA;Yang SJ;Oldenburg JE;Exline CM;Guatelli JC;Cannon PM
通讯作者：
Cannon PM