Open forum infectious diseases · 2025
Whole-Genome Sequencing of Hepatitis B Virus Genotypes E and A in Zambia Reveals Limited Viral Diversity in HIV Coinfection.
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Vinikoor Michael J, Walker Andreas, Nsokolo Bright, Musonda Taonga, Muula Guy, Michailidis Eleftherios, Wandeler Gilles, Alatrakchi Nadia, Kelly Paul, Damagnez Maximillian, Le Duyen Bao, Voges Anja, Lübke Nadine, Kanunga Annie, Bosomprah Samuel, Bhattacharya Debika, Chibundi Carolyn, Bwalya Given, Musukuma-Chifulo Kalo, Suslov Aleksei, Feuerherd Martin, Heim Markus H, Schwartz Robert E, Chung Raymond T, Lauer Georg, Sinkala Edford, Timm Jörg
Аннотация
BACKGROUND: The molecular characteristics of hepatitis B virus (HBV) in Africa, including the impact of HIV coinfection, are poorly understood.
METHODS: We performed whole-genome sequencing (WGS) on biospecimens collected before antiviral therapy in a well-characterized cohort of adults with HBV in Zambia, enriched for HIV coinfection (HBV/HIV). We assessed the frequency of basal core promoter (BCP) and precore variants, substitution frequencies, and the ratio of nonsynonymous to synonymous substitutions (dN/dS ratios), a surrogate for selection pressure.
RESULTS: Among 215 participants (median age, 33 years; 36% e antigen [HBeAg] positive, 35% with HBV/HIV), 114 (53.0%) had viral genotype E (gtE), and 101 (47.0%) had genotype A (gtA), subgenotype 1. BCP and precore variants, associated with HBeAg negativity, were more common with increased age, in the absence of HIV, and with gtE. Distinct from gtA, gtE had dN/dS ratios that were increased in the core vs polymerase region. Low dN/dS ratios were observed in HBV/HIV, especially at the lowest CD4 T-cell frequencies. Sequences from acute HBV infection as well as from 5 participants with chronic HBV/HIV who cleared hepatitis B surface antigen early during tenofovir-based antiretroviral therapy showed remarkably low dN/dS ratios.
CONCLUSIONS: HBV gtE exhibited distinct substitution patterns compared with gtA, and HBV/HIV was associated with reduced HBV sequence diversity, consistent with impaired immune pressure.
METHODS: We performed whole-genome sequencing (WGS) on biospecimens collected before antiviral therapy in a well-characterized cohort of adults with HBV in Zambia, enriched for HIV coinfection (HBV/HIV). We assessed the frequency of basal core promoter (BCP) and precore variants, substitution frequencies, and the ratio of nonsynonymous to synonymous substitutions (dN/dS ratios), a surrogate for selection pressure.
RESULTS: Among 215 participants (median age, 33 years; 36% e antigen [HBeAg] positive, 35% with HBV/HIV), 114 (53.0%) had viral genotype E (gtE), and 101 (47.0%) had genotype A (gtA), subgenotype 1. BCP and precore variants, associated with HBeAg negativity, were more common with increased age, in the absence of HIV, and with gtE. Distinct from gtA, gtE had dN/dS ratios that were increased in the core vs polymerase region. Low dN/dS ratios were observed in HBV/HIV, especially at the lowest CD4 T-cell frequencies. Sequences from acute HBV infection as well as from 5 participants with chronic HBV/HIV who cleared hepatitis B surface antigen early during tenofovir-based antiretroviral therapy showed remarkably low dN/dS ratios.
CONCLUSIONS: HBV gtE exhibited distinct substitution patterns compared with gtA, and HBV/HIV was associated with reduced HBV sequence diversity, consistent with impaired immune pressure.