Kumthip Kattareeya, Chusri Pattranuch, Pantip Chansom, Thongsawat Satawat, O'Brien Amornrat, Maneekarn Niwat
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200 Thailand.
Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, 50200 Thailand.
Virusdisease. 2016 Mar;27(1):55-62. doi: 10.1007/s13337-015-0300-x. Epub 2016 Jan 18.
Mutations in several regions of HCV genome are shown to correlate with response to interferon (IFN) treatment. Persistence of HCV infection and poor susceptibility to treatment might be contributed by mutations arising within HCV genome which enable the virus to escape from host immune response/IFN treatment. This study investigated mutations in core and NS5A genes of HCV from non-responder and relapser patients after treatment with Peg-IFN-α and ribavirin. Viral RNA was extracted from patient sera and core and NS5A genes were amplified by RT-PCR. Nucleotide sequences of the core and NS5A genes were determined by direct sequencing, and converted to amino acid sequences. Nucleotide and amino acid sequences in the core region, ISDR, PKRBD, and V3 regions within NS5A after treatment were highly conserved when comparing to their corresponding sequences obtained before treatment. Interestingly, when comparing the virus from relapsers to those from non-responders, the number of mutations after treatment in N-terminal region of NS5A of virus from relapsers was significantly higher than those from non-responders (P < 0.05). Amino acid mutations at the N-terminus of NS5A of the virus in relapsers might help the virus to survive and somehow relapse after the cessation of the treatment.
丙型肝炎病毒(HCV)基因组多个区域的突变显示与干扰素(IFN)治疗反应相关。HCV基因组内出现的突变可能导致HCV感染持续存在且对治疗的敏感性较差,这些突变使病毒能够逃避宿主免疫反应/IFN治疗。本研究调查了聚乙二醇干扰素-α(Peg-IFN-α)和利巴韦林治疗后无反应者和复发者的HCV核心基因和NS5A基因中的突变。从患者血清中提取病毒RNA,通过逆转录聚合酶链反应(RT-PCR)扩增核心基因和NS5A基因。通过直接测序确定核心基因和NS5A基因的核苷酸序列,并转化为氨基酸序列。与治疗前获得的相应序列相比,治疗后核心区域、NS5A内的干扰素敏感决定区(ISDR)、蛋白激酶R结合域(PKRBD)和V3区域的核苷酸和氨基酸序列高度保守。有趣的是,将复发者的病毒与无反应者的病毒进行比较时,复发者病毒NS5A N端区域治疗后的突变数量显著高于无反应者(P<0.05)。复发者病毒NS5A N端的氨基酸突变可能有助于病毒存活,并在治疗停止后以某种方式复发。