Characterization of small genomic regions of the hepatitis B virus should be performed with more caution

Abstract

BackgroundHepatitis 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.MethodsFifty-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.ResultsJpHMM 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12985-018-1100-x) contains supplementary material, which is available to authorized users.

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

“…Evidence increasingly supports a role for HBV genotype in influencing disease progression, including risk of developing chronic infection, e-antigen seroconversion, transmission mode and the development of hepatocellular carcinoma [7,8]. Studies often refer to 'wild-type' virus [8,9], but wild-type for one genotype may not reflect consensus for other genotypes [10,11]. Understanding the diverse range of HBV strains circulating globally, and their associations with disease, will allow us to move towards a more specific and precise approach to analysis.…”

“…S1, available in the online version of this article); however, the number of sequences covering the full genome lags a long way behind sequences for single genes or shorter fragments. To date, numerous subtyping misclassifications have been documented for HBV, predominantly driven by the use of partial genome sequences rather than full-length genomes [9,10], the inappropriate classification of recombinant strains [11] and publications redesignating same subgenotype classifications to distinctly different strains [12,13]. Whilst a number of HBV sequence and analysis resources already exist, including HBVdb [14], HBVRegDB [15], HBVDR [16] and geno2pheno (https:// hbv.…”

Hepatitis B virus preS2Δ38–55 variants: A newly identified risk factor for hepatocellular carcinoma

“…In addition, as patients with HCC in SSA present at advanced stages, we were unable to recruit individuals with early small tumours, and all patients had tumours >5 cm (data not shown). Finally, whilst our partial HBV sequences (surface genes) are sufficient for genotyping, 3,4 they are not for sub-genotyping as numerous misclassifications will arise, [42][43][44] and this issue needs to be resolved in future studies.…”

The Function of some Important TCM and Iranian Medicinal Plants in Treatment of Viral Hepatitis

“…The global burden of disease due to acute hepatitis B and C and to cancer and cirrhosis of the liver is high and is forecast to become a higher ranked cause of death over the next two decades. [1][2][3][4][5] Because hepatitis A, B, C, D and E viruses vary in their global distribution and routes of transmission, prevention strategies need to be considered. 6 Hepatitis B virus infection early in life is related to the highest risk of chronic infection, and people with chronic infection risk progress to cirrhosis of the liver and primary liver cancer.…”