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Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

ABSTRACT: Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors' plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. An analysis of the genetic diversity of eight HBV small surface genes from our 16 samples was conducted and compared with HBV sequences from NCBI of 164 international (non-Australian) blood donors. Genotypes A-D were identified in our samples. The region of HBV small surface gene that contained the sequence encoding the 'a' determinant had a greater genetic diversity than the remaining part of the gene. No escape mutants or OBI-related variants were observed in our samples. Variant call analysis revealed two samples with a nucleotide deletion leading to truncation of polymerase and/or large/middle surface amino acid sequences. Overall, we found that HBV small surface gene sequences from Australian donors demonstrated a lower level of genetic diversity than those from non-Australian donor population included in the study.

SUBMITTER: Phan NMH

PROVIDER: S-EPMC8310342 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

Phan Ngoc Minh Hien NMH Faddy Helen M HM Flower Robert L RL Dimech Wayne J WJ Spann Kirsten M KM Roulis Eileen V EV

Viruses 20210630 7

Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors' plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. ...[more]

PMID: 34208852

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Project description:The rapid spread of HBV has resulted in the emergence of new variants. These viral genotypes and variants, in addition to carcinogenic risk, can be key predictors of therapy response and outcomes. As a result, a better knowledge of these emerging HBV traits will aid in the development of a treatment for HBV infection. However, many Sub-Saharan African nations, including Kenya, have insufficient molecular data on HBV strains circulating locally. This study conducted a population-genetics analysis to evaluate the genetic diversity of HBV among Kenyan blood donors. In addition, within the same cohort, the incidence and features of immune-associated escape mutations and stop-codons in Hepatitis B surface antigen (HBsAg) were determined. In September 2015 to October 2016, 194 serum samples were obtained from HBsAg-positive blood donors residing in eleven different Kenyan counties: Kisumu, Machakos, Uasin Gishu, Nairobi, Nakuru, Embu, Garissa, Kisii, Mombasa, Nyeri, and Turkana. For the HBV surface (S) gene, HBV DNA was isolated, amplified, and sequenced. The sequences obtained were utilized to investigate the genetic and haplotype diversity within the S genes. Among the blood donors, 74.74% were male, and the overall mean age was 25.36 years. HBV genotype A1 (88.14%) was the most common, followed by genotype D (10.82%), genotype C (0.52%), and HBV genotype E (0.52%). The phylogenetic analysis revealed twelve major clades, with cluster III comprising solely of 68 blood donor isolates (68/194-35.05%). A high haplotype diversity (Hd = 0.94) and low nucleotide diversity (π = 0.02) were observed. Kisumu county had high number of haplotypes (22), but low haplotype (gene) diversity (Hd = 0.90). Generally, a total of 90 haplotypes with some consisting of more than one sequence were observed. The gene exhibited negative values for Tajima's D (-2.04, p<0.05) and Fu's Fs (-88.84). Several mutations were found in 139 isolates, either within or outside the Major Hydrophilic Area (MHR). There were 29 mutations found, with 37.9% of them situated inside the "a" determinant. The most common mutations in this research were T143M and K122R. Escape mutations linked to diagnostic failure, vaccination and immunoglobulin treatment evasion were also discovered. Also, one stop-codon, W163STP, inside the MHR, was found in one sample from genotype A. In Kenya, HBV/A1 is still the most common genotype. Despite limited genetic and nucleotide diversity, haplotype network analysis revealed haplotype variance among HBV genotypes from Kenyan blood donors. The virological properties of immune escape, which may be the source of viral replication endurance, were discovered in the viral strains studied and included immune-escape mutations and stop-codon. The discovery of HBsAg mutations in MHR in all isolates highlighted the need of monitoring MHR mutations in Kenya.

Project description:BackgroundTransfusion Transmitted Infections (TTIs) are still a growing public health problem in Africa. Studies that synthesize the available evidence on the seroprevalence of Hepatitis B Surface Antigen (HBsAg) among African blood donors are scarce. Therefore, this study aimed to synthesize qualitatively and quantitatively the seroprevalence of Hepatitis B Virus Surface Antigen (HBsAg) among blood donors in Africa.MethodsWe conducted a systematic review and meta-analysis where we included all studies that reported the seroprevalence of HBsAg among blood donors in Africa. The references were searched from electronic databases: PubMed, Web of Science, Cochrane, Scopus, WHO research database-HINARI, Global Index Medicus and ClinicalTrials.gov. We further analyzed the full list of references of all included studies. The pooled seroprevalence was estimated through random effect model. The heterogeneity was assessed through Cochrane's Q test and I 2, respectively. Meta-regression, subgroup and sensitivity analyses were conducted.ResultsWe obtained 124 studies that met our inclusion criteria, comprising 3,573,211 blood donors tested for HBsAg. The pooled seroprevalence of HBsAg among blood donors in Africa was 6.93% (95% CI: 5.95-7.97%; I 2 = 100%; p < 0.001). We found that the heterogeneity was explained by the study performed country and, African region. The higher prevalence was observed in Western 10.09% (95% CI: 8.75-11.50%), Central 7.81% (95% CI: 5.34-10.71%), and Eastern African region 4.87% (95% CI: 3.77-6.11%) and lower prevalence were observed in Southern 2.47% (95% CI: 0.54-5.75%) followed by Northern Africa region with 1.73% (95% CI: 0.45-3.79%). Additionally, based on the date of publication, we found that the highest prevalence was observed in studies published between 2001 and 2010 (9.41, 95% CI: 7.19-11.90) and the lowest prevalence was observed in studies published between 2011 and 2024 (6.26%; 95% CI: 5.19-7.42).ConclusionThe seroprevalence of HBsAg among blood donors in Africa is still very high and heterogeneous. Therefore, intensifying the screening and vaccination of the population for Hepatitis B is critical to ensure blood safety toward eliminating Hepatitis B in Africa.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=395616, PROSPERO CRD42023395616.

Dataset Information

Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

Publications

Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

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