Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV-1 chronic infection
Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV-1 chronic infection
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鉴定与 HIV-1 慢性感染临床参数相关的两种独特的自然发生的 Vpr 序列多态性
DOI：
10.1002/jmv.24612
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发表时间：
2017
影响因子：
12.7
通讯作者：
Ueno Takamasa
中科院分区：
文献类型：
--
作者：
Kamori Doreen;Hasan Zafrul;Ohashi Jun;Kawana-Tachikawa Ai;Gatanaga Hiroyuki;Oka Shinichi;Ueno Takamasa
HIV-1病毒蛋白R（Vpr）在HIV-1复制中起重要作用。尽管鉴定了许多HLA I类相关的免疫逃逸突变;但免疫驱动的Vpr多态性是否与疾病结局相关尚不清楚。因此，我们通过使用从444名HLA分型、未经治疗的慢性HIV-1感染者中分离的血浆病毒RNA，全面分析了Vpr序列多态性及其与疾病结局和宿主HLA基因型的相关性。Vpr第13、37、45、55、63、77、84、85、86和93位氨基酸残基与患者的血浆病毒载量和/或CD 4计数显著相关。进一步分析显示，55位的Ala与较低的血浆病毒载量显著相关; 63位的Thr与较低的血浆病毒载量和较高的CD 4计数显著相关。此外，位于功能重要的α螺旋结构域的两个位置的氨基酸残基数量与血浆病毒载量呈负相关，与CD 4计数呈正相关。此外，一种遗传学校正的方法揭示了位置55和63处的残基与患者的HLA基因型相关。总而言之，我们的结果表明，功能重要和免疫反应位点的Vpr多态性可能至少部分有助于体内病毒复制和疾病结局。J. Med. Virol。89：123-129，2017.© 2016 Wiley Periodicals，Inc.
HIV‐1 viral protein R (Vpr) plays important roles in HIV‐1 replication. Despite the identification of a number of HLA class I‐associated immune escape mutations; it is yet known whether immune‐driven Vpr polymorphisms are associated with disease outcome. Hereby, we comprehensively analyzed Vpr sequence polymorphisms and their association with disease outcome and host HLA genotypes, by using plasma viral RNA isolated from 444 HLA‐typed, treatment‐naïve, chronically HIV‐1 infected individuals. Vpr amino acid residues at positions 13, 37, 45, 55, 63, 77, 84, 85, 86, and 93 were significantly associated with patients’ plasma viral load and/or CD4 count. Further analysis revealed Ala at position 55 was significantly associated with lower plasma viral load; and Thr at position 63 was significantly associated with lower plasma viral load and higher CD4 count. Also, the number of amino acid residues at the two positions, located in a functionally important α‐helical domain, correlated inversely with plasma viral load and positively with CD4 count. Moreover, a phylogenetically corrected method revealed residues at positions 55 and 63 are associated with patients’ HLA genotypes. Taken together, our results suggest that Vpr polymorphisms at functionally important and immune‐reactive sites may contribute, at least in part, to viral replication and disease outcome in vivo.J. Med. Virol. 89:123–129, 2017. © 2016 Wiley Periodicals, Inc.