Institute of Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, Mexico.
J Med Virol. 2015 Jun;87(6):985-92. doi: 10.1002/jmv.24098. Epub 2015 Mar 2.
Long-term treatment with retrotranscriptase (RT) inhibitors eventually leads to the development of drug resistance. Drug-related mutations occur naturally and these can be found in hepatitis B virus (HBV) carriers who have never received antiviral therapy. HBsAg are overlapped with RT domain, thus nucleot(s)ide analogues (NAs) resistance mutations and naturally-occurring mutations can cause amino acid changes in the HBsAg. Twenty-two patients with chronic hepatitis B were enrolled; three of them were previously treated with NAs and 19 were NAs-naïve treated. HBV reverse transcriptase region was sequenced; genotyping and analysis of missense mutations were performed in both RT domain and HBsAg. There was predominance of genotype H. Drug mutations were present in 18.2% of patients. Classical lamivudine resistance mutations (rtM204V/rtL180M) were present in one naïve-treatment patient infected with genotype G. New amino acid changes were identified in drug resistance sites in HBV strains from patients infected with genotype H; rtQ215E was present in two naïve-NAs treatment patients and rtI169M was identified in a patient previously treated with lamivudine. Mutations at sites rt169, rt204, and rt215 resulted in the Y161C, I195M, and C206W mutations at HBsAg. Also, new amino acid changes were identified in B-cell and T-cell epitopes and were more frequent in HBsAg compared to RT domain. In conclusion, new amino acid changes at antiviral resistance sites, B-cell and T-cell epitopes in HBV genotype H were identified in Mexican patients.
长期使用逆转录酶 (RT) 抑制剂最终会导致耐药性的产生。药物相关的突变是自然发生的，这些突变可以在从未接受过抗病毒治疗的乙型肝炎病毒 (HBV) 携带者中发现。HBsAg 与 RT 结构域重叠，因此核苷酸类似物 (NA) 耐药突变和自然发生的突变会导致 HBsAg 中的氨基酸变化。共纳入 22 例慢性乙型肝炎患者；其中 3 例曾接受过 NA 治疗，19 例为 NA 初治患者。对 HBV 逆转录酶区进行测序；对 RT 结构域和 HBsAg 中的错义突变进行基因分型和分析。主要基因型为 H。18.2%的患者存在耐药突变。1 例基因型 G 初治患者存在经典拉米夫定耐药突变（rtM204V/rtL180M）。在感染基因型 H 的患者的 HBV 株中，在耐药部位鉴定出新的氨基酸变化；2 例初治 NA 治疗患者存在 rtQ215E，1 例拉米夫定治疗前患者存在 rtI169M。rt169、rt204 和 rt215 位点的突变导致 HBsAg 中 Y161C、I195M 和 C206W 突变。此外，在 B 细胞和 T 细胞表位中还鉴定出了新的氨基酸变化，与 RT 结构域相比，HBsAg 中更频繁出现新的氨基酸变化。总之，在墨西哥患者的 HBV 基因型 H 中鉴定出了抗病毒耐药部位、B 细胞和 T 细胞表位的新氨基酸变化。
