Moradi Abdolvahab, Zhand Sareh, Ghaemi Amir, Javid Naeme, Tabarraei Alijan
Infectious Diseases Research Centre, Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Virus Genes. 2012 Jun;44(3):382-7. doi: 10.1007/s11262-012-0715-z. Epub 2012 Jan 25.
Mutations of HBsAg especially within the "a" determinant could alter the antigenicity of the protein causing failure of HBsAg neutralization and escaping from the host's immune system, resulting in active viral replication and liver disease. This project aimed to investigate mutation in the S gene region of HBV infected patients in Golestan Province-Iran. HBV-DNA extractions from plasma and PCR of 100 patients were performed. Direct sequencing and alignment of S gene were applied using reference sequence from Gene Bank database. All isolates were belonged to genotype D, subgenotype D1, subtype ayw2. Overall 92 point mutations occurred. Of them, 40 (43.47%) were missense and 52 (56.52%) were silent. Mutations were detected in 95 cases (95%). Five of 40 mutations (12.5%) occurred in "a" determinant and 13 (32.5%), 17 (42.5%), and 2 (5%) were seen in antigenic epitope regions of B cell, CD(4)(+) and CTL, respectively. Frame shift mutations were seen in 22 cases (22%). 14% of mutations occurred at Major Hydrophilic Region(MHR) area which P120T/S and R122K/T substitutions were the most frequent ones (4%). Mutation in G145R of the S gene was observed in one case. A large number of MHR mutants are in association with failure of HBsAg detection, vaccine, and immunotherapy escape. This study showed "a" determinant S gene mutations in HBV infected people with HBsAg positivity in Golestan Province-Iran. The rate of mutation in our study was 95%. Collectively, the results of this project exhibited that most of mutations were clustered in CD(4)(+) antigenic epitopes.
乙肝表面抗原（HBsAg）的突变，尤其是在“a”决定簇内的突变，可能会改变该蛋白的抗原性，导致HBsAg中和失败并逃避免疫系统，从而引发病毒的活跃复制和肝脏疾病。本项目旨在调查伊朗戈勒斯坦省乙肝病毒（HBV）感染患者S基因区域的突变情况。对100例患者的血浆进行了HBV-DNA提取及PCR检测。利用基因库数据库中的参考序列对S基因进行直接测序和比对。所有分离株均属于D基因型、D1亚基因型、ayw2亚型。总共发生了92个点突变。其中，40个（43.47%）为错义突变，52个（56.52%）为沉默突变。在95例（95%）中检测到了突变。40个突变中有5个（12.5%）发生在“a”决定簇，在B细胞、CD4+和CTL的抗原表位区域分别观察到13个（32.5%）、17个（42.5%）和2个（5%）突变。在22例（22%）中发现了移码突变。14%的突变发生在主要亲水区（MHR）区域，其中P120T/S和R122K/T替换最为常见（4%）。在1例中观察到S基因的G145R突变。大量MHR突变体与HBsAg检测失败、疫苗接种失败及免疫治疗逃逸相关。本研究显示了伊朗戈勒斯坦省HBsAg阳性的HBV感染人群中S基因“a”决定簇的突变情况。我们研究中的突变率为95%。总体而言，该项目的结果表明，大多数突变集中在CD4+抗原表位。
