Lei Jia1, Fengyu Hu2, Hanping Li1, Lin Li1, Xiaoping Tang2, Yongjian Liu1, Haohui Deng2, Jingwan Han1, Jingyun Li3, Weiping Cai4. 1. Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. 2. Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, Guangdong, China. 3. Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. lijy@bmi.ac.cn. 4. Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, Guangdong, China. gz8hcwp@126.com.
Abstract
BACKGROUND: Hepatitis B virus is a hepatotropic DNA virus that reproduces via an RNA intermediate. It can lead to an increased risk of serious liver diseases such as hepatocellular carcinoma and is a serious threat to public health. Currently, the HBV are designated based on greater than 8% nucleotide variation along the whole genome. The recombination of HBV is very common, a large majority of which are recombinants between 2 genotypes. The current work aims to characterize a suspected recombinant involving 3 genotypes. METHODS: Fifty-seven HBV full-genome sequences were obtained from 57 patients co-infected with HBV and HIV-1 by amplification coupled with sequencing. JpHMM and RDP4 were used to perform recombination analysis respectively. The recombination results of a suspected 3-genotypic recombinant were further confirmed by both maximum likelihood phylogenetic tree and Mrbayes tree. RESULTS: JpHMM recombination analysis clearly indicated one 3-genotypic HBV recombinant composing of B/C/D. The genotype assignments are supported by significant posterior probabilities. The subsequent phylogenetic analysis of sub-regions derived from inferred breakpoints led to a disagreement on the assignment of D segment. Investigating the conflict, further exploration by RDP4 and phylogenies revealed that the jpHMM-derived 3-genotypic recombinant is actually a B/C genotypic recombinant with C fragment spanning 1899 to 2295 (jpHMM) or 1821 to 2199 (RDP4). CONCLUSIONS: The whole analysis indicated that (i) determination of small genomic regions should be performed with more caution, (ii) combinations of various recombination detection approaches conduce to obtain impartial results, and (iii) a unified system of nomenclature of HBV genotypes is necessary.
BACKGROUND:Hepatitis B virus is a hepatotropic DNA virus that reproduces via an RNA intermediate. It can lead to an increased risk of serious liver diseases such as hepatocellular carcinoma and is a serious threat to public health. Currently, the HBV are designated based on greater than 8% nucleotide variation along the whole genome. The recombination of HBV is very common, a large majority of which are recombinants between 2 genotypes. The current work aims to characterize a suspected recombinant involving 3 genotypes. METHODS: Fifty-seven HBV full-genome sequences were obtained from 57 patients co-infected with HBV and HIV-1 by amplification coupled with sequencing. JpHMM and RDP4 were used to perform recombination analysis respectively. The recombination results of a suspected 3-genotypic recombinant were further confirmed by both maximum likelihood phylogenetic tree and Mrbayes tree. RESULTS: JpHMM recombination analysis clearly indicated one 3-genotypic HBV recombinant composing of B/C/D. The genotype assignments are supported by significant posterior probabilities. The subsequent phylogenetic analysis of sub-regions derived from inferred breakpoints led to a disagreement on the assignment of D segment. Investigating the conflict, further exploration by RDP4 and phylogenies revealed that the jpHMM-derived 3-genotypic recombinant is actually a B/C genotypic recombinant with C fragment spanning 1899 to 2295 (jpHMM) or 1821 to 2199 (RDP4). CONCLUSIONS: The whole analysis indicated that (i) determination of small genomic regions should be performed with more caution, (ii) combinations of various recombination detection approaches conduce to obtain impartial results, and (iii) a unified system of nomenclature of HBV genotypes is necessary.
Entities:
Keywords:
Genotypic recombination; Hepatitis B virus; JpHMM; RDP4
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