Arginine insertion and loss of N-linked glycosylation site in HIV-1 envelope V3 region confer CXCR4-tropism.
Arginine insertion and loss of N-linked glycosylation site in HIV-1 envelope V3 region confer CXCR4-tropism.
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DOI：
10.1038/srep02389
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发表时间：
2013
影响因子：
4.6
通讯作者：
Gatanaga, Hiroyuki
中科院分区：
文献类型：
--
作者：
Tsuchiya, Kiyoto;Ode, Hirotaka;Hayashida, Tsunefusa;Kakizawa, Junko;Sato, Hironori;Oka, Shinichi;Gatanaga, Hiroyuki
HIV-1包膜糖蛋白gp 120的第三可变区（V3）在决定病毒辅助受体的使用（嗜性）中起关键作用。然而，V3中哪些突变组合赋予向性转变仍不清楚。在未接受过抗逆转录病毒治疗的HIV-1患者中观察到一种独特的突变模式，与HIV-1嗜性从CCR 5向CXCR 4的转变相关。通过细胞-细胞融合试验和重组HIV-1变异体的表型分析证实，在11位插入精氨酸和N-连接糖基化位点的缺失是获得纯CXCR 4嗜性所必需的。在另外53名CD 4+细胞计数<200/mm 3的患者中，有2名（3.8%）发现了相同的V3突变模式和相关的嗜性转移。精氨酸插入和N-连接糖基化位点缺失的结合通常赋予CXCR 4嗜性。认识到这一规律将有助于确认常规规则对V3序列的向性预测。
The third variable region (V3) of HIV-1 envelope glycoprotein gp120 plays a key role in determination of viral coreceptor usage (tropism). However, which combinations of mutations in V3 confer a tropism shift is still unclear. A unique pattern of mutations in antiretroviral therapy-naive HIV-1 patient was observed associated with the HIV-1 tropism shift CCR5 to CXCR4. The insertion of arginine at position 11 and the loss of the N-linked glycosylation site were indispensable for acquiring pure CXCR4-tropism, which were confirmed by cell-cell fusion assay and phenotype analysis of recombinant HIV-1 variants. The same pattern of mutations in V3 and the associated tropism shift were identified in two of 53 other patients (3.8%) with CD4+ cell count <200/mm3. The combination of arginine insertion and loss of N-linked glycosylation site usually confers CXCR4-tropism. Awareness of this rule will help to confirm the tropism prediction from V3 sequences by conventional rules.
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