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中国广东 HIV-1 CRF55_01B 的遗传多样性和耐药性。

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China.

机构信息

Institute of AIDS Control and Prevention, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.

Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.

出版信息

Curr HIV Res. 2020;18(3):210-218. doi: 10.2174/1570162X18666200415140652.

DOI:10.2174/1570162X18666200415140652
PMID:32294040
Abstract

BACKGROUND

HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade's polymorphisms in its functionally critical regions protease and reverse transcriptase.

OBJECTIVE

To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B's drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition.

METHODS

HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively.

RESULTS

A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE's. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples.

CONCLUSION

CRF55_01B's pol has different genetic diversity comparing to its counterpart in CRF55_01B's parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

摘要

背景

HIV-1 CRF55_01B 于 2013 年首次报告。目前,尚无关于其功能关键区域蛋白酶和逆转录酶中多态性的报告。

目的

鉴定 CRF55_01B 与亲本 clade CRF01_AE 和亚型 B 之间蛋白酶和逆转录酶的多样性差异;并研究与蛋白酶抑制和逆转录酶抑制相关的 CRF55_01B 耐药突变。

方法

从男男性行为者人群的血浆中提取 HIV-1 RNA。采用我们的内部 PCR 程序进行逆转录和巢式 PCR 扩增。根据多态性分析和 HIV 耐药性数据库的使用,分别确定基因分型和耐药相关突变和多态性。

结果

鉴定的 CRF55_01B 序列中共有 9.24% 具有主要耐药性。CRF55_01B 包含与 CRF01_AE 不同的 I13I/V、G16E 和 E35D 原发性耐药突变。RT 区的 11 个多态性中有 7 个与 CRF01_AE 不同。在 RT 区还发现了另外三个多态性,R211K(98.3%)、F214L(98.3%)和 V245A/E(98.3%),与亚型 B 不同。所有 CRF55_01B 序列均发现 V179E/D 突变,负责 100%潜在低水平耐药性。最后,系统进化分析显示,18 个不同的聚类占样本的 35%。

结论

CRF55_01B 的 pol 与 CRF55_01B 的亲本 clade 中的 pol 相比具有不同的遗传多样性。CRF55_01B 具有较高的原发性耐药性,V179E/D 突变可能使其更容易产生耐药性。

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