Hossain Md Golzar, Ueda Keiji
1Division of Virology, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
2Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh.
Infect Agent Cancer. 2019 Nov 7;14:33. doi: 10.1186/s13027-019-0253-6. eCollection 2019.
Hepatitis B caused by HBV is a serious public health hazard prevalent worldwide including Bangladesh. Few scattered molecular studies of HBV have been reported in Bangladesh. This study aimed to analyze the genetic variability of RT/HBsAg overlapping region of HBV isolates of Bangladesh and determination of correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations.
A total of 97 complete HBsAg sequences of Bangladeshi HBV isolates from 2005 to 2017 from NCBI GenBank were extracted and analyzed using several HBV bioinformatics tools such as Geno2pheno-HBV, HBV Serotyper, HIV-Grade:HBV-Tool, and CLC sequence viewer.
The prevalence of genotypes A, C, and D are 18, 46 and 35% which correspond to serotype , , and respectively. The prevalence of HBsAg escape mutations is 51% and most of which (62%) are found in the genotype D followed by 32% in genotype C and 6% in genotype A. Interestingly most (24/36) of the sequences of HBsAg escape mutations contained 128 V mutant which all belongs to only serotype (Genotype D). Prevalence of drug-resistant mutations is ~ 11%, most of which are from genotype C (63.64%) and D (36.36%). Lamivudine resistant mutations were found in ~ 11% of sequences followed by Telbivudine 10% and Adefovir 3% where Tenofovir showed susceptibility to all 97 sequences. Moreover, 7 among of 97 sequences showed both HBsAg and drugs resistant mutations and none of them are found due to the same nucleotide substitutions.
There is a strong correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations. This meta-analytical review will be helpful for genotype-serotype prediction by PCR-based diagnosis and development of vaccine and/or diagnostic kits, and the treatment against HBV infection in the future.
由乙肝病毒(HBV)引起的乙型肝炎是一种严重的公共卫生危害,在包括孟加拉国在内的全球范围内普遍存在。孟加拉国仅有少量关于HBV的零散分子研究报道。本研究旨在分析孟加拉国HBV分离株逆转录酶/乙肝表面抗原(RT/HBsAg)重叠区域的基因变异性,并确定基因型/血清型与HBsAg逃逸和/或耐药突变之间的相关性。
从NCBI基因库中提取了2005年至2017年孟加拉国HBV分离株的97条完整HBsAg序列,并使用多种HBV生物信息学工具进行分析,如Geno2pheno-HBV、HBV血清型分析器、HIV-Grade:HBV-Tool和CLC序列查看器。
基因型A、C和D的流行率分别为18%、46%和35%,分别对应血清型 、 和 。HBsAg逃逸突变的流行率为51%,其中大部分(62%)出现在基因型D中,其次是基因型C中的32%和基因型A中的6%。有趣的是,大多数(24/36)HBsAg逃逸突变序列包含128V突变体,这些突变体均仅属于血清型 (基因型D)。耐药突变的流行率约为11%,其中大部分来自基因型C(63.64%)和D(36.36%)。在约11%的序列中发现了拉米夫定耐药突变,其次是替比夫定10%和阿德福韦3%,而替诺福韦对所有97条序列均敏感。此外,97条序列中有7条同时显示出HBsAg和耐药突变,且没有一条是由相同的核苷酸替换导致的。
基因型/血清型与HBsAg逃逸和/或耐药突变之间存在很强的相关性。这一荟萃分析综述将有助于通过基于PCR的诊断进行基因型-血清型预测,以及疫苗和/或诊断试剂盒的开发,以及未来针对HBV感染的治疗。