Al-Qahtani Ahmed Ali, Rubino Salvatore, Al-Ahdal Mohammed N
Molecular Virology and Infectious Diseases section, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Saudi Arabia.
J Infect Dev Ctries. 2011 May 28;5(5):370-6. doi: 10.3855/jidc.1806.
Hepatitis C virus (HCV), which is a major cause of liver diseases worldwide, undergoes genetic variation during the course of infection. The aim of this study was to examine sequence variations within the HVR1 region of HCV genotype 4 in infected Saudi patients treated with a combination therapy of interferon-α and ribavirin.
cDNA of the HVR1 region of HVC-4 from one responder and one non-responder patients was generated, cloned and sequenced. Ten clones were randomly selected and analyzed for changes in nucleotide and amino acid sequences before the start of treatment, and subsequently three and six months after the start of the therapy course.
Based on nucleotide and amino acid sequence variations, the HVR1 region is highly sequence variable. In both the responder and the non-responder patients, amino acid sequence variations were observed and a clear distinction between patients was evident. The amino acid changes after the treatment course were different in the responder compared to the non-responder subject. Five amino acids (residues 364 to 367, 381 and 409) were unique in the non-responder patient.
Considerable amino acid variations were observed in the HVR1 region in both responder and non-responder patients. These findings could have implications for the development of an HCV vaccine as well as treatment protocols for HCV infections.
丙型肝炎病毒(HCV)是全球肝脏疾病的主要病因之一,在感染过程中会发生基因变异。本研究的目的是检测接受α干扰素和利巴韦林联合治疗的沙特感染患者中HCV 4型HVR1区域内的序列变异。
从一名治疗有反应者和一名无反应者患者中获取HCV-4的HVR1区域的cDNA,进行克隆和测序。在治疗开始前、治疗开始后三个月和六个月,随机选择十个克隆并分析其核苷酸和氨基酸序列的变化。
基于核苷酸和氨基酸序列变异,HVR1区域具有高度的序列变异性。在有反应者和无反应者患者中均观察到氨基酸序列变异,且患者之间有明显区别。与无反应者相比,有反应者在治疗过程后的氨基酸变化不同。无反应者患者中有五个氨基酸(第364至367位、381位和409位残基)是独特的。
在有反应者和无反应者患者的HVR1区域均观察到相当大的氨基酸变异。这些发现可能对HCV疫苗的开发以及HCV感染的治疗方案有影响。