Liu Xiaoqing, Chen Zhiwei, Tang Qiao, Hu Peng
Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Virus Erad. 2022 Jun 15;8(2):100071. doi: 10.1016/j.jve.2022.100071. eCollection 2022 Jun.
Patients infected with hepatitis C (HCV) genotype (GT) 3, especially GT3b, are still difficult to cure. GT3b is more common than GT3a in southwestern China. Here we aimed to investigate the prevalence of naturally occurring RASs in HCV GT3 in southwestern China and performed phylogenetic analysis.
Serum samples were collected from patients with HCV GT3 infection. Sanger sequencing was used to validate resistance-associated substitutions (RASs). Phylogenetic analysis was performed using MEGA X and the observed-minus-expected-squared algorithm was used to analyze amino acid covariance.
A total of 136 patients were enrolled, including 41 HCV GT3a and 95 GT3b infected patients. In the NS5A region, the proportion of RASs found in GT3b (99%) was notably higher than in GT3a (9%). In the NS3 region, RASs prevalence in GT3b (5%) was lower than in GT3a (24%). NS5B-specific RASs were rare. Both the NS5A30k and L31 M substitutions occurred in 96% of GT3b sequences. The A30K + L31M combination was found in 94% of GT3b isolates, however, there were no A30K or L31M mutations observed in the GT3a sequence.
Significant differences were observed between HCV GT3a and GT3b in terms of RAS prevalence. The origin of GT3a appears to be more diverse compared with GT3b in southern China. Studies specifically aimed at HCV GT3b infection should be initiated to gain more insight into this subtype.
丙型肝炎病毒（HCV）基因3型（GT）感染者，尤其是GT3b感染者，目前仍难以治愈。在中国西南部，GT3b比GT3a更为常见。本研究旨在调查中国西南部HCV GT3自然发生的耐药相关位点（RASs）的流行情况，并进行系统发育分析。
收集HCV GT3感染患者的血清样本。采用桑格测序法验证耐药相关替代位点（RASs）。使用MEGA X进行系统发育分析，并采用观察值减去期望值平方算法分析氨基酸协方差。
共纳入136例患者，其中41例为HCV GT3a感染者，95例为GT3b感染者。在NS5A区域，GT3b中发现的RASs比例（99%）显著高于GT3a（9%）。在NS3区域，GT3b中RASs的流行率（5%）低于GT3a（24%）。NS5B特异性RASs罕见。NS5A30k和L31M替代均出现在96%的GT3b序列中。94%的GT3b分离株中发现A30K + L31M组合，然而，在GT3a序列中未观察到A30K或L31M突变。
HCV GT3a和GT3b在RAS流行率方面存在显著差异。在中国南方，GT3a的起源似乎比GT3b更多样化。应开展针对HCV GT3b感染的专门研究，以更深入了解该亚型。
