Investigation of mutations in the partial sequences of the surface and polymerase genes of hepatitis B virus associated with immune escape and drug resistance in HIV-infected patients

对乙型肝炎病毒表面基因和聚合酶基因部分序列突变与HIV感染患者的免疫逃逸和耐药性相关的研究

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Abstract

BACKGROUND: Co-infection of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has an impact on high HBV replication and progression to liver cancer. These may lead to cross-resistance of drugs due to natural mutations or therapeutic pressure. These require continuous monitoring of HBV variants for better diagnosis and treatment strategies. METHODS: Convenience sampling was used to collect fifty archival sera from Inkosi Albert Luthuli Central Hospital. Sera were subjected to HBsAg screening using ELISA, DNA extraction, PCR amplification, Sanger sequencing, genotype prediction and mutation analysis. RESULTS: Of the 50 samples, 86% (43/50) were HBsAg positive; 82% (41/50) PCR positive with 92% (38/41) sequenced and only 26 sequences were subjected to molecular characterization. The HBV sequences showed similarity to genotype A (73% [19/26]), genotypes G (5% [3/26]) and genotype C (15% [4/26]). Prevalence of the mutations in the surface region was (47% [18/38]); including diagnostic failure (K122R and T143S) and immune escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). The mutations in the RT were at (36% [14/38]) with drug resistance mutations (DRM) at (50% [7/14]). Mutations showed resistance to lamivudine (LMV) at (35% [5/14]), telbivudine (LdT) at (29% [4/14]), (14% [2/14]) for entecavir (ETV) and (21% [3/14]) for adefovir (ADV). One sample had a combination of L180M, M204V, S202K, and M250I mutations. CONCLUSIONS: Our findings highlight the prevalence of HBV genotype A in HIV-infected patients in South Africa. The study provides evidence of mutations linked to immune evasion and drug resistance; this infers that these mutations may have clinical implications for the diagnosis and treatment of HBV in HBV/HIV co-infected individuals. Further in vitro studies must be conducted to explore the impact of the identified mutation on the surface protein expression during diagnosis; phenotype impact of the mutant virus towards the antiviral drugs.

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