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Natural prevalence of NS3 gene resistance-associated substitutions (RASs) in patients with chronic hepatitis C from the state of Pará/Brazil
Virus Research ( IF 5 ) Pub Date : 2020-11-28 , DOI: 10.1016/j.virusres.2020.198251
Desirée Lopes da Silva 1 , Heloisa Marceliano Nunes 1 , Pedro Eduardo Bonfim Freitas 1
Affiliation  

The resistance of hepatitis C virus (HCV) to direct-acting antiviral agents, used in chronic hepatitis C treatment, consists of a natural process resulting from resistance-associated substitutions (RASs) at specific amino acid regions. To identify and establish the natural prevalence of RASs in the NS3 gene in patients with chronic hepatitis C in the state of Pará, northern Brazil. Molecular analysis was performed on a total of 35 patients infected with HCV genotype 1, who were treatment-naive to protease inhibitors. HCV RNA was extracted from plasma and the NS3 region was amplified and submitted to DNA sequencing (Sanger). The general natural prevalence of RASs in the NS3 gene was 37.5 % (Y56F and S122T). The substitutions Y56F (34.3 %), S122T (3.1 %), V132I (15.6 %) and V170I (9.3 %) were identified. Y56F and S122T provide resistance to the protease inhibitors grazoprevir and simeprevir, respectively. All amino acid substitutions in the NS3 gene, including RASs, identified in patients from the state of Pará were present in other Brazilian studies. The natural presence of RASs in this study reflects the elevated genetic variability of HCV.



中文翻译:

来自巴西帕拉州的慢性丙型肝炎患者中 NS3 基因耐药相关取代 (RAS) 的自然流行

丙型肝炎病毒 (HCV) 对用于慢性丙型肝炎治疗的直接作用抗病毒药物的耐药性由特定氨基酸区域的耐药性相关取代 (RAS) 引起的自然过程组成。确定并确定巴西北部帕拉州慢性丙型肝炎患者 NS3 基因中 RAS 的自然患病率。对总共 35 名感染 HCV 基因 1 型的患者进行了分子分析,这些患者对蛋白酶抑制剂未进行过治疗。从血浆中提取 HCV RNA,扩增 NS3 区域并进行 DNA 测序(Sanger)。NS3 基因中 RAS 的一般自然流行率为 37.5%(Y56F 和 S122T)。鉴定出取代 Y56F (34.3 %)、S122T (3.1 %)、V132I (15.6 %) 和 V170I (9.3 %)。Y56F 和 S122T 分别对蛋白酶抑制剂 grazoprevir 和 simeprevir 产生抗性。在帕拉州的患者中发现的 NS3 基因中的所有氨基酸取代,包括 RAS,在其他巴西研究中都存在。本研究中 RAS 的自然存在反映了 HCV 的遗传变异性升高。

更新日期:2020-12-04
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