Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses
Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses
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CRF55_01B 病毒中 HIV-1 逆转录酶中 V179E 的自然存在和 E138G 的流行率上升
DOI：
10.1016/j.meegid.2019.104098
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发表时间：
2020-01-01
影响因子：
3.2
通讯作者：
Li, Lin
中科院分区：
文献类型：
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作者：
Liu, Yongjian;Li, Hanping;Li, Lin
越来越多的证据表明，自然发生的HIV-1遗传多样性可能对耐药性产生影响。最近，我们先前的研究已经证明了HIV-1 CRF65_cpx毒株中V179 D和K103 R/V179 D突变的自然存在与对非核苷逆转录酶抑制剂（NNRTI）的耐药性相关。本研究的目的是调查在中国流行的其他HIV-1亚型或CRF中是否存在天然耐药突变（DRM）。从Los Alamos HIV序列数据库中共检索到14，403条来自中国的pol序列，其中10，041条未经治疗，并呈现出显著的遗传多样性。除了在CRF65_cpx中天然存在V179 D和K103 R/V179 D之外，在CRF55_01B中发现天然存在V179 E。在228例感染CRF55_01B的患者中，除1例外，所有患者均存在NNRTI耐药突变V179 E，在14例初治患者中检测到V179 E和E138 G联合突变，发生率为6.2%。观察到CRF55_01B菌株中E138 G突变患病率随时间增加的显著趋势（p <0.001）。对CRF55_01B菌株进行系统发育分析，以明确其流行病学关系。E138 G突变序列大多分布在CRF55_01B大簇中，表明E138 G的流行主要是由多个突变事件引起的，而不是E138 G突变的局部传播簇。我们的研究结果强调了对CRF55_01B菌株进行分子监测的重要性，以及迫切需要实施有效的预防措施以减少CRF55_01B的传播。
There is increasing evidence that naturally occurring HIV-1 genetic diversity can have an impact on drug resistance. Recently, our previous study has demonstrated the natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF65_cpx strains. The aim of this study is to investigate the presence of natural drug-resistance mutations (DRMs) in other HIV-1 subtypes or CRFs circulating in China. A total of 14,403 pol sequences from China were retrieved from the Los Alamos HIV Sequence Database, 10,041 of which were treatment naive and presented substantial genetic diversity. Besides the natural presence of V179D and K103R/V179D in CRF65_cpx, the natural presence of V179E was found in CRF55_01B. In all but one of the 228 patients infected with CRF55_01B, NNRTI resistance mutation V179E was present and the combination of V179E and E138G was detected in 14 treatment-naive patients, with a rate of 6.2%. A significant trend for increasing prevalence of E138G mutation in CRF55_01B strains over time was observed (p < .001). Phylogenetic analysis was conducted to clarify the epidemiological relationship of CRF55_01B strains. Most of the sequences containing E138G mutation scattered in the big CRF55_01B cluster, which indicated the rising prevalence of E138G was mainly due to multiple mutation events rather than local transmission clusters of a particular variant containing E138G mutation. Our findings highlight the importance of molecular surveillance of CRF55_01B strains and the urgent need for implementation of effective preventive measures to reduce the transmission of CRF55_01B.