In silico analysis of mutations associated with occult hepatitis B virus (HBV) infection in South Africa

Olagbenro, Matthew; Anderson, Motswedi; Gaseitsiwe, Simani; Powell, Eleanor A.; Gededzha, Maemu P.; Selabe, Selokela G.; Blackard, Jason T.

doi:10.1007/s00705-021-05196-7

Cited by 3 publications

(1 citation statement)

References 78 publications

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“…Forty-five OBI-related point mutations were identified in Pre-S1, Pre-S2, S, Core, and Pol genes, because their frequency in OBIs was significantly higher than that in the controls ( P < 0.05; Table 3 and Supplementary Table S2 ). Among them, 26 mutations have been documented in previous studies (Supplementary Table S2 ) 14 , 16 , 20 , 28 , 29 , while the other 19 mutations were novel findings, including E39K/D and S101T in Pre-S1 gene, Q10R in Pre-S2 gene, P178Q, Q181R, and I226N in the S gene, T147A in Core gene in OBI B and T118K in S gene in OBI C (Table 3 ).…”

Section: Resultsmentioning

confidence: 86%

Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China

Wang

Huang

et al. 2022

Sci Rep

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The characteristics of a large sample size of the full-length genome of occult hepatitis B virus (HBV) infection (OBI) have not been extensively explored in China. Voluntary blood donors who were HBsAg-negative/HBV NAT-positive (HBsAg−/HBV NAT+) were identified by blood screening and recruited. Blood samples were tested for HBV serologic markers, viral loads, and PCR to identify OBI. HBV full-length genomes were obtained by amplifying two fragments using nested PCR. The characterization of OBI strains was based on sequence analyses compared with HBsAg+ strains obtained from the same donor population. Of the 50 full-length genomes of 172 identified OBI strains, 33 were classified as genotype B (OBIB) and 17 strains as genotype C (OBIC). Significantly higher nucleotide variabilities were observed in the Pre-S2/S promoter region (SP2) and core upstream regulatory sequence (CURS) in OBIB than in their HBsAg+ controls (P < 0.05). Both OBIB and OBIC showed higher amino acid (aa) variabilities in Pol and Pre-S/S regions than their controls (P < 0.05). In addition, 19 novel OBI-related mutations were found spanning the four open reading frames (ORFs) of the HBV genome. Four novel deletions and one novel insertion were also found in OBIC strains. Several novel OBI-related mutations spanning the four ORFs of the virus were identified by characterizing a large sample size of the full-length OBI genome, which may affect the production of HBsAg and contribute to the occult infection of HBV.

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Section: Resultsmentioning

confidence: 86%

Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China

Wang

Huang

et al. 2022

Sci Rep

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Molecular Characterization of Hepatitis B Virus in People Living with HIV in Rural and Peri-Urban Communities in Botswana

Phinius,

Choga,

Anderson

et al. 2024

Biomedicines

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(1) Background: Hepatitis B virus (HBV) sequencing data are important for monitoring HBV evolution. We aimed to molecularly characterize HBV sequences from participants with HBV surface antigen-positive (HBsAg+) serology and occult hepatitis B infection (OBI+). (2) Methods: We utilized archived plasma samples from people living with human immunodeficiency virus (PLWH) in Botswana. HBV DNA was sequenced, genotyped and analyzed for mutations. We compared mutations from study sequences to those from previously generated HBV sequences in Botswana. The impact of OBI-associated mutations on protein function was assessed using the Protein Variation Effect Analyzer. (3) Results: Sequencing success was higher in HBsAg+ than in OBI+ samples [86/128 (67.2%) vs. 21/71 (29.2%)]. Overall, 93.5% (100/107) of sequences were genotype A1, 2.8% (3/107) were D3 and 3.7% (4/107) were E. We identified 13 escape mutations in 18/90 (20%) sequences with HBsAg coverage, with K122R having the highest frequency. The mutational profile of current sequences differed from previous Botswana HBV sequences, suggesting possible mutational changes over time. Mutations deemed to have an impact on protein function were tpQ6H, surfaceV194A and preCW28L. (4) Conclusions: We characterized HBV sequences from PLWH in Botswana. Escape mutations were prevalent and were not associated with OBI. Longitudinal HBV studies are needed to investigate HBV natural evolution.

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Frequency of drug resistance and immune escape mutations in the hepatitis B virus genome detected in pregnant women in the Republic of Guinea

Balde

Ostankova

Boumbaly

et al. 2023

Problems of Virology

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The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea. Materials and methods. Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus. Results and discussion. In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified. Conclusion. The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

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In silico analysis of mutations associated with occult hepatitis B virus (HBV) infection in South Africa

Cited by 3 publications

References 78 publications

Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China

Molecular characteristics of the full-length genome of occult hepatitis B virus from blood donors in China

Molecular Characterization of Hepatitis B Virus in People Living with HIV in Rural and Peri-Urban Communities in Botswana

Frequency of drug resistance and immune escape mutations in the hepatitis B virus genome detected in pregnant women in the Republic of Guinea

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