Whole-Genome Sequencing of Hepatitis B Virus Genotypes E and A in Zambia Reveals Limited Viral Diversity in HIV Coinfection.
Publisher DOI
PubMed ID
41200694
Abstract
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.
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.
Date Issued
2025-11
Publication Type
Article
Subjects
hepatitis B virus
•
human immunodeficiency virus
•
sub-Saharan Africa
•
viral sequencing
Language(s)
en
Author(s)
Vinikoor, Michael J | |
Walker, Andreas | |
Nsokolo, Bright | |
Musonda, Taonga | |
Muula, Guy | |
Michailidis, Eleftherios | |
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 |
Additional Credits
Journal
Open Forum Infectious Diseases
Publisher
Oxford University Press
ISSN
2328-8957
Access(Rights)
open.access