A Genetic Variant of Hepatitis B Virus Divergent from Known Human and Ape Genotypes Isolated from a Japanese Patient and Provisionally Assigned to New Genotype J

Abstract

Hepatitis B virus (HBV) of a novel genotype (J) was recovered from an 88-year-old Japanese patient with hepatocellular carcinoma who had a history of residing in Borneo during the World War II. It was divergent from eight human (A to H) and four ape (chimpanzee, gorilla, gibbon, and orangutan) HBV genotypes, as well as from a recently proposed ninth human genotype I, by 9.9 to 16.5% of the entire genomic sequence and did not have evidence of recombination with any of the nine human genotypes and four nonhuman genotypes. Based on a comparison of the entire nucleotide sequence against 1,440 HBV isolates reported, HBV/J was nearest to the gibbon and orangutan genotypes (mean divergences of 10.9 and 10.7%, respectively). Based on a comparison of four open reading frames, HBV/J was closer to gibbon/orangutan genotypes than to human genotypes in the P and large S genes and closest to Australian aboriginal strains (HBV/C4) and orangutan-derived strains in the S gene, whereas it was closer to human than ape genotypes in the C gene. HBV/J shared a deletion of 33 nucleotides at the start of preS1 region with C4 and gibbon genotypes, had an S-gene sequence similar to that of C4, and expressed the ayw subtype. Efficient infection, replication, and antigen expression by HBV/J were experimentally established in two chimeric mice with the liver repopulated for human hepatocytes. The HBV DNA sequence recovered from infected mice was identical to that in the inoculum. Since HBV/J is positioned phylogenetically in between human and ape genotypes, it may help to trace the origin of HBV and merits further epidemiological surveys.Worldwide, an estimated 400 million people are infected with hepatitis B virus (HBV) persistently, of whom three quarters live in the Southeast and Far East Asia, and one million die of decompensated cirrhosis and/or hepatocellular carcinoma (HCC) annually (8,15). HBV is the smallest animal DNA virus and has a genome made of approximately 3,200 nucleotides (nt) that contains four open reading frames for P, C, S, and X genes; they code for DNA polymerase/reversetranscriptase, core protein, surface protein, and X protein, respectively (49). The S gene is divided into preS1 and preS2 regions and the small S gene, and the C gene splits into PreC and C.Eight genotypes of HBV have been recognized by a sequence divergence of Ͼ8% in the entire genome and named by capital alphabet letters (A to H) in the order of discovery (3,26,29,42). HBV genotypes are further classified into subgenotypes, such as B1/Bj and B2-5/Ba (44), as well as C1/Cs, C2/Ce, and C3-5 (36). A systematic nomenclature is proposed for designating HBV subgenotypes using Arabic numbers, such as A1, A2, and A3 (25). HBV genotypes have distinct geographical distribution (16,23). Genotype A is prevalent in Africa, Europe and India, genotypes B and C are common in Asia, and genotype E is common in sub-Saharan Africa. Genotypes F and H are restricted to Central and South American continents, whereas genotype D is distributed all over the world. HBV genot...

A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from recombination between genotypes D and E, is circulating in Niger along with HBV/E strains

“…Recently, a ninth genotype isolated in Laos (Olinger et al, 2008a) and Vietnam (Hannoun et al, 2000;Olinger et al, 2008b;Tran et al, 2008) and tentatively termed 'I' was proposed, although it is still subject to debate (Kurbanov, 2008). In addition, a tenth genotype provisionally termed genotype 'J' was isolated from a Japanese patient (Tatematsu et al, 2009). Further extensive phylogenetic analyses of HBV genotypes in different studies worldwide have resulted in recognition of several subgenotypes within genotypes, A (A1-A5), B (B1-B8), C (C1-C7), D (D1-D7) and F (F1-F4), defined by .…”

Molecular Evolution of Hepatitis Viruses

“…In addition, a new genotype I has been proposed for a recombinant of genotypes A, C, and G mainly found in Laos and Vietnam (Tran et al, 2008), genotype J for a recombinant strain between human and ape viruses (Tatematsu et al, 2009). Indeed, several studies have pointed that recombination seems to play an important role in shaping the evolution of HBV (Fares & Holmes, 2002;Simmonds & Midgley, 2005).…”

Prevalence and Risk Factors of Hepatitis B Virus Genotype D Amongst Inmates in Alborz Province, Iran: A Cross-Sectional Survey

“…Eight major genotypes (A-H) with several subtypes and two additional isolated genotypes (genotype I in Vietnam and genotype J in Japan) are defined by insertions or deletions of nucleotides, but with less than 10% overall variation among them (6)(7)(8). Genotyping of HBV isolates from different parts of the world have shown a distinct geographical distribution even within a region.…”