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初治印度尼西亚乙肝病毒(HBV)携带者中乙肝病毒逆转录酶和重叠表面基因的突变谱

Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers.

作者信息

Yamani Laura Navika, Yano Yoshihiko, Utsumi Takako, Wasityastuti Widya, Rinonce Hanggoro Tri, Widasari Dewiyani Indah, Lusida Maria Inge, Hayashi Yoshitake

机构信息

Institute of Tropical Disease, Airlangga University.

Center for Infectious Diseases, Kobe University Graduate School of Medicine.

出版信息

Jpn J Infect Dis. 2017 Nov 22;70(6):647-655. doi: 10.7883/yoken.JJID.2017.078. Epub 2017 Oct 31.

DOI:10.7883/yoken.JJID.2017.078
PMID:29093313
Abstract

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naïve Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P < 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

摘要

乙型肝炎病毒(HBV)基因组逆转录酶(RT)区域的突变是治疗效果不佳的一个重要因素。尽管如此,此前在印度尼西亚分离出的HBV毒株中这些突变的流行情况尚未得到系统研究。因此,在本研究中,我们调查了初治印度尼西亚HBV携带者病毒中RT区域的突变情况以及这些突变与表面蛋白氨基酸变化之间的关联。总体而言,从美国国立生物技术信息中心检索到96个全长印度尼西亚HBV基因组序列(B基因型,n = 54;C基因型,n = 42)。在6/54(11.1%)的B基因型毒株和1/42(2.4%)的C基因型毒株中发现了自然发生的原发性和/或补偿性耐药突变。两种基因型中对核苷(酸)类似物耐药的潜在突变和/或治疗前突变更为常见,但C基因型毒株比B基因型毒株更常见。RT基因中的A - B结构域间区域在C基因型中比在B基因型中更频繁发生突变(3.51 ± 2.53对1.08 ± 1.52,P<0.001)。了解RT基因的突变情况和表面蛋白的变化可能有助于临床医生为印度尼西亚HBV感染的管理选择最合适的抗病毒药物以及疫苗接种或乙肝免疫球蛋白方案。

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