Wang Y, Wu H Y, Zhao X C, Zhu W P, Wan Q, Lu Y H, Jiang Q W
Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China.
Shanghai Pudong New District Center for Disease Control and Prevention, Shanghai 200120, China; Fudan University Pudong Institute of Preventive Medicine, Shanghai 200120, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2017 Mar 10;38(3):378-383. doi: 10.3760/cma.j.issn.0254-6450.2017.03.021.
To understand the genotypes of hepatitis C virus (HCV) circulating in intravenous drug users (IDUs) in Pudong new district, Shanghai, and explore the population growth and selection pressure of the HCV strains isolated. A total of 200 serum specimens sampled from IDUs in local methadone maintenance treatment clinic in Pudong were used for amplification of a HCV NS5B 377-nt partial sequence. Mean evolutionary rate and effective number of infections were estimated based on the 377-nt partial sequences of the HCV strains isolated from IDUs and isolated contemporarily from local voluntary blood donors, men who have sex with men and reported hepatitis C cases by using BEAST software. Selection pressure sites were identified with online Datamonkey software for subsequent comparison with direct-acting antiviral (DAA) drug binding sites. A total of 39 (19.5%) serum specimens were positive for HCV RNA. The genotypes were determined based on the HCV NS5B 377-nt partial sequences as follows: subtype 3a (=14), 3b (=13), 1b (=7), 6a (=4) and 6n (=1). The partial sequences of the HCV strains isolated in IDUs shared high homology with the sequences of the HCV strains isolated in other populations. The Bayesian Skyline Plot indicated that the estimated infections with HCV subtype 1b increased exponentially during the 1990s, whereas that of subtypes 3a and 3b increased slowly since the mid-1990s. In the NS5B 377-nt partial sequences of the HCV strains isolated in IDUs, there were two positive selection sites and seventy-eight negative selection sites recognized. The mutation rate was as low as 2.2% in the 377-nt partial sequences corresponding to the known seven DAA drug binding sites. HCV subtype 3a and 3b were the predominant genotypes in the IDUs in Pudong. Subtype 1b was prevalent in different populations and evolved very rapidly, and more infections might be caused, suggesting further attention to its prevention, control and treatment. Although DAA treatment based on HCV NS5B binding sites targeting local IDUs might be effective, it is still necessary to strengthen the surveillance.
为了解上海市浦东新区静脉吸毒者（IDU）中丙型肝炎病毒（HCV）的基因型，探讨分离出的HCV毒株的群体增长和选择压力。从浦东新区当地美沙酮维持治疗诊所的IDU中采集的200份血清标本用于扩增HCV NS5B 377核苷酸部分序列。基于从IDU中分离出的HCV毒株以及同时从当地自愿献血者、男男性行为者和报告的丙型肝炎病例中分离出的毒株的377核苷酸部分序列，使用BEAST软件估计平均进化率和有效感染数。使用在线Datamonkey软件确定选择压力位点，以便随后与直接作用抗病毒（DAA）药物结合位点进行比较。共有39份（19.5%）血清标本HCV RNA呈阳性。根据HCV NS5B 377核苷酸部分序列确定基因型如下：3a亚型（=14）、3b亚型（=13）、1b亚型（=7）、6a亚型（=4）和6n亚型（=1）。IDU中分离出的HCV毒株的部分序列与其他人群中分离出的HCV毒株的序列具有高度同源性。贝叶斯天际线图表明，估计1b亚型HCV感染在20世纪90年代呈指数增长，而3a和3b亚型自20世纪90年代中期以来增长缓慢。在IDU中分离出的HCV毒株的NS5B 377核苷酸部分序列中，识别出两个正选择位点和78个负选择位点。在对应于已知7个DAA药物结合位点的377核苷酸部分序列中，突变率低至2.2%。HCV 3a和3b亚型是浦东新区IDU中的主要基因型。1b亚型在不同人群中普遍存在且进化非常迅速，可能导致更多感染，提示需进一步关注其预防、控制和治疗。尽管基于针对当地IDU的HCV NS5B结合位点的DAA治疗可能有效，但仍有必要加强监测。
