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Review
. 2014 Jun 21;20(23):7152-68.
doi: 10.3748/wjg.v20.i23.7152.

Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions

Mahmoud Reza Pourkarim  1 , Samad Amini-Bavil-Olyaee  1 , Fuat Kurbanov  1 , Marc Van Ranst  1 , Frank Tacke  1
Affiliations
Review

Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions

Mahmoud Reza Pourkarim et al. World J Gastroenterol. .

Abstract

The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.

Keywords: Classification; Genotype; Hepatitis; Hepatitis B virus; Phylogenetic tree; Subgenotype.

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Figures

Figure 1
Figure 1
Neighbour-joining phylogenetic tree was conducted based on hepatitis B virus full-length genomes of all proposed genotypes and subgenotypes before (A) and after (B) reclassification. HBV genome sequence that used are listed below: JN182318: A1; HE576989: A2; AB194951: A3; AY934764: A4; FJ692613: A5; GQ331047: A6; FN545833: A7; AB642091: B1; FJ899779: B2; GQ924617: B3; GQ924626: B4; GQ924640: B5; JN792893: B6; GQ358137: B7; GQ358147: B8; GQ358149: B9; AB697490: C1; GQ358158: C2; DQ089801: C3; HM011493: C4; EU410080: C5; EU670263: C6; GU721029: C7; AP011106: C8; AP011108: C9; AB540583: C10; AB554019: C11; AB554025: C12; AB644280: C13; AB644284: C14; AB644286: C15; AB644287: C16; GU456636: D1; GQ477452: D2; EU594434: D3; GQ922003: D4; GQ205377: D5; KF170740: D6; FJ904442: D7; FN594770: D8; JN664942: D9; FN594748: E; FJ709464: F1b; DQ899146: F2b; AY090459: F1a; DQ899142: F2a; AB036920: F3; AF223965: F4; GU563556: G; AB516393: H; FJ023659: I1; FJ023664: I2 ; AB486012: J and AY226578: Woolly monkey as an out-group. HBV: Hepatitis B virus.
Figure 2
Figure 2
The time line of identification and designation of hepatitis B virus subgenotypes.
Figure 3
Figure 3
Geographical distribution of hepatitis B virus genotypes and subgenotypes in different regions of the world. Yellow arrows illustrate the directions of HBV subgenotype dispersal through immigration from highly and intermediate endemic countries to low HBV endemic areas (map of hepatitis B surface antigen (HBsAg) prevalence adapted from the website of the WHO). HBV: Hepatitis B virus; WHO: World Health Organization.
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