Laboratório de Biologia Molecula, Divisão Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu, SP, Brasil.
Mem Inst Oswaldo Cruz. 2013 Feb;108(1):13-7. doi: 10.1590/s0074-02762013000100002.
The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.
治疗慢性丙型肝炎的目标是实现持续病毒学应答，这是指在治疗后至少 6 个月血清中检测不到丙型肝炎病毒（HCV）RNA 水平。然而，目前的治疗方法仅对 50%感染 HCV 基因型 1 的患者有效，该基因型在巴西最为流行。因此，开发了非结构蛋白 3（NS3）丝氨酸蛋白酶抑制剂来提高 HCV 感染患者的反应。然而，耐药变异体的出现一直是治疗成功的主要障碍。本研究的目的是评估 37 例未接受蛋白酶抑制剂治疗的 HCV 基因型 1 感染患者的 NS3 基因组区 HCV 中是否存在耐药突变和遗传多态性。使用血浆病毒 RNA 扩增和测序 HCV NS3 基因。结果表明催化三联体是保守的。在密码子 153、40 和 91 观察到大量取代；还检测到耐药变异体 T54A、T54S、V55A、R155K 和 A156T。本研究表明，在未接受蛋白酶抑制剂治疗的患者的 HCV NS3 区存在耐药突变和遗传多态性，这些数据对于确定巴西新型药物的疗效非常重要。
