Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E

Abstract

Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC. Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E. Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described. Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques. Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands. Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.

Contemporary and historical human migration patterns shape hepatitis B virus diversity

“…2019 ; Pronier et al. 2020 ; Olusola et al. 2021 ), and undetectable levels of genome amplification without antigen production have raised concerns about cryptic movement of specific HBV genotypes from countries of high endemicity to those of low endemicity ( Zhu et al.…”

“…Importantly, we identified clinically and para-clinically related mutations at ORF S, as previously described ( Mak and Kramvis 2020 ; Lin et al. 2021 ; Olusola et al. 2021 ).…”

Molecular diversity of hepatitis B virus among pregnant women in Amhara National Regional State, Ethiopia

“…Furthermore, mutations related to antiviral therapy were detected in 6/46 (13.0%), triple mutations rtV173L, rtL180M, and rtM204V resistant to lamivudine, double mutation; rtL180M and rtM204V, resistant to entecavir and M204V resistant to telbivudine in one pregnant woman whom was on ART drugs. Similarly, studies reported drug resistance mutation among drug naïve and in HIV-infected patients in Ethiopia and Nigeria [ 21 , 24 , 26 , 54 ]. Surprisingly, we have isolated R153W and N248H mutations in this study similarly a study done in Nigeria [ 54 ].…”

“…Similarly, studies reported drug resistance mutation among drug naïve and in HIV-infected patients in Ethiopia and Nigeria [ 21 , 24 , 26 , 54 ]. Surprisingly, we have isolated R153W and N248H mutations in this study similarly a study done in Nigeria [ 54 ]. These R153W and N248H drug resistance mutations were not detected in previous studies in Ethiopia.…”

“…Interestingly, in the present study, 19/46 (41.3%) of amino acid substitution were identified in MHR of HBV S gene and nearly half of the mutation were observed in “a” determinant region. Similarly, studies reported mutations of MHR of surface gene among blood donors, HIV-infected and chronic liver patients in Ethiopia [ 24 – 26 , 54 ]. This implies that mutation in MHR and “a” determinant region may pose a challenge on some commercial serological diagnosis of HBV and vaccine escape on the community.…”