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Molecular characterization of occult hepatitis B virus in genotype E-infected subjects

Chengyao Li^2,

Jillian Temple^1,

¹ Division of Transfusion Medicine, Department of Haematology, University of Cambridge, Cambridge, UK
² National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK
³ Department of Obstetrics and Gynaecology, Komfo Anokye Teaching Hospital, Kumasi, Ghana
⁴ Transfusion Medicine Unit, Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana

Correspondence
Jean-Pierre Allain
jpa1000{at}cam.ac.uk

Occult hepatitis B virus (HBV) infection (OBI), defined as the presence of HBV DNA without detectable HBV surface antigen (HBsAg), is frequent in west Africa, where genotype E is prevalent. The prevalence of OBI in 804 blood donors and 1368 pregnant women was 1.7 and 1.5 %, respectively. Nine of 32 OBI carriers were evaluated with HBV serology, viral load and complete HBV genome sequence of two to five clones. All samples except one were anti-HBV core antigen-positive and three contained antibodies against HBsAg (anti-HBs). All strains were of genotype E and formed quasispecies with 0.20–1.28 % intra-sample sequence variation. Few uncommon mutations (absent in 23 genotype E reference sequences) were found across the entire genome. Two mutations in the core region encoded truncated or abnormal capsid protein, potentially affecting viral production, but were probably rescued by non-mutated variants, as found in one clone. No evidence of escape mutants was found in anti-HBs-carrying samples, as the ‘a’ region was consistently wild type. OBI carriers constitute approximately 10 % of all HBV DNA-viraemic adult Ghanaians. OBI carriers appear as a disparate group, with a very low viral load in common, but multiple origins reflecting decades of natural evolution in an area essentially devoid of human intervention.

Present address: Institute of Virology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, PR China.

Present address: Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Cambridge, UK.

The GenBank/EMBL/DDBJ accession numbers for the nucleotide sequences analysed in this study are EU239217–EU239226.

A supplementary table showing primers used for sequencing full-length HBV amplicons is available with the online version of this paper.

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