scholarly journals Complex structural variations in non-human primate hepatitis B virus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yoshihito Nagura ◽  
Kei Fujiwara ◽  
Kentaro Matsuura ◽  
Etsuko Iio ◽  
Yasuhito Tanaka ◽  
...  

Abstract Background Recent genome sequence technology has revealed a novel type of genetic rearrangement referred to as complex structural variations (SVs). Previous studies have elucidated the complex SVs in human hepatitis B viruses (HBVs). In this study, we investigated the existence of complex SVs in HBVs from non-human primates (NHPs). Methods Searches for nucleotide sequences of NHP HBV were conducted using the PubMed, and genetic sequences were retrieved from databases. The candidate genetic sequences harboring complex SVs were analyzed using the CLUSTALW program and MAFFT. Additional bioinformatical analyses were performed to determine strains with complex SVs and to elucidate characteristics of NHP HBV strains. Results One hundred and fifty-four HBV strains from NHPs were identified from databases. SVs and complex SVs were observed in 11 (7.1%) strains. Three gibbon HBV (GiHBV) strains showed complex SVs consisting of an insertion and a deletion in the pre-S1 region. One GiHBV strain possessed a 6-nt insertion, which are normally specific to human HBV genotype A (HBV/A) in the Core region, and further analyses clarified that the 6-nt insertion was not caused by recombination, but rather by simple insertion. Another chimpanzee HBV strain showed complex SVs in the pre-S1 region, which were composed of human HBV/E, G-specific polymorphic SV, and an additional 6-nt insertion. Conclusions In this study, complex SVs were observed in HBV strains from NHPs, in addition to human HBV strains, as shown in previous studies. These data suggest that complex SVs could also be found in other members of hepadnaviruses, and may play a role in their genetic diversity.

1986 ◽  
Vol 6 (5) ◽  
pp. 1393-1400
Author(s):  
M J Roossinck ◽  
S Jameel ◽  
S H Loukin ◽  
A Siddiqui

We studied the expression of the core region of the hepatitis B virus genome in mammalian cells with recombinant plasmid vectors. Stably transformed rat fibroblast cell lines were established by transfection with vectors containing subgenomic and genome-length hepatitis B virus DNA, followed by G418 selection. The RNA transcripts directed by the core region were characterized by Northern blot hybridization and S1 nuclease mapping. Using the chloramphenicol acetyltransferase gene expression system, the promoter activity located upstream of the core open reading frame was confirmed. The synthesis of core and e polypeptides was studied with a commercial radioimmunoassay. These studies show that partial deletion of the precore sequences abolished secretion of the e antigen, but there was pronounced synthesis of the core antigen in transfected cells.


Microbiology ◽  
2000 ◽  
Vol 81 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Lieven Stuyver ◽  
Sija De Gendt ◽  
Caroline Van Geyt ◽  
Fabien Zoulim ◽  
Michael Fried ◽  
...  

The hepatitis B virus (HBV) genotype was determined in a total of 121 plasma samples collected in France and the US from patients chronically infected with HBV. HBV genotype A was predominant in this collection, appearing in 66 samples (54%), while genotypes B, C, D, E and F occurred in 4 (3%), 14 (12%), 23 (19%), 1 (1%) and 0 (0%) of samples, respectively. However, the genotype of a total of 13 (11%) samples (2 from France, 11 from the US) could not be determined with the methodology used. Sequence analysis, and subsequent phylogenetic analysis of the complete genome and the individual open reading frames, showed that the virus isolate from these samples was 3248 bp long and, phylogenetically, did not cluster with any of the known genotypes. This strain was provisionally called HBV genotype G. Virus isolates that were obtained from geographically separated regions like France and the US were closely related to each other. All virus strains analysed contained some characteristic differences when compared to genotype A: a translational stop codon at aa 2 and 28 of the preCore region; a 36 nt (12 aa) insert in the amino-terminal part of the Core antigen (HBcAg); a 2 aa deletion in the carboxy-terminal part of HBcAg; and a 1 aa deletion in the preS1 open reading frame. The deduced amino acid sequence of HBsAg suggests that this newly discovered genotype G strain belongs to serological group adw2.


2004 ◽  
Vol 78 (14) ◽  
pp. 7575-7581 ◽  
Author(s):  
Izumi Hasegawa ◽  
Yasuhito Tanaka ◽  
Anna Kramvis ◽  
Takanobu Kato ◽  
Fuminaka Sugauchi ◽  
...  

ABSTRACT The eight genotypes of hepatitis B virus (HBV) have different geographical distributions, virological characteristics, and clinical manifestations. A unique subtype of HBV genotype A (HBV/A) was reported in sub-Saharan Africa, raising the possibility that patients infected with this subtype (HBV/Aa [“a” for African and Asian]) may have different clinical outcomes than other HBV/A isolates (HBV/Ae [“e” for European]). Comparison between 30 HBV/Aa and 30 HBV/Ae isolates indicated that almost all HBV/Ae isolates had G at nucleotide (nt) 1809 and C at nt 1812, whereas HBV/Aa isolates had T1809/T1812. Taking advantage of these two single nucleotide polymorphisms (SNPs), a novel subtype-specific PCR assay in the X/precore/core region was developed. This assay was combined with a restriction fragment length polymorphism assay using BglII in a different region (nt 1984 to 1989), which has a SNP distinguishing HBV/Aa from HBV/Ae, resulting in 100% specificity for the combined assay. Application of the subtyping assay using sera from 109 paid donors in the United States indicated significantly different distributions of HBV/A subtypes among races; African-Americans, Caucasians, and Hispanics had HBV/Ae, whereas Asians had mainly HBV/Aa, suggesting that the HBV/Aa isolates may have been imported by recent immigration from Asia. In conclusion, the specificity and sensitivity of the combined subtyping assay were confirmed, and its usefulness was demonstrated in a practical context.


2006 ◽  
Vol 80 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Michael Guarnieri ◽  
Kyun-Hwan Kim ◽  
Genie Bang ◽  
Jisu Li ◽  
Yonghong Zhou ◽  
...  

ABSTRACT The pregenomic RNA directs replication of the hepatitis B virus (HBV) genome by serving both as the messenger for core protein and polymerase and as the genome precursor following its packaging into the core particle. RNA packaging is mediated by a stem-loop structure present at its 5′ end designated the ε signal, which includes the core gene initiator AUG. The precore RNA has a slightly extended 5′ end to cover the entire precore region and, consequently, directs the translation of a precore/core protein, which is secreted as e antigen (HBeAg) following removal of precore-derived signal peptide and the carboxyl terminus. A naturally occurring G1862T mutation upstream of the core AUG affects the bulge of the ε signal and generates a “forbidden” residue at the −3 position of the signal peptide cleavage site. Transfection of this and other mutants into human hepatoma cells failed to prove their inhibition of HBeAg secretion but rather revealed great impairment of genome replication. This replication defect was associated with reduced expression of core protein and could be overcome by a G1899A covariation, or by nonsense or frameshift mutation in the precore region. All these mutations antagonized the G1862T mutation on core protein expression. Cotransfection of the G1862T mutant with a replication-deficient HBV genome that provides core protein in trans also restored genome replication. Consistent with our findings in cell culture, HBV genotype A found in African/Asian patients has T1862 and is associated with much lower viremia titers than the European subgroup of genotype A.


1997 ◽  
Vol 32 (5) ◽  
pp. 668-671 ◽  
Author(s):  
Tsutomu Sato ◽  
Junji Kato ◽  
Johji Kawanishi ◽  
Katsuhisa Kogawa ◽  
Masami Ohya ◽  
...  

1986 ◽  
Vol 6 (5) ◽  
pp. 1393-1400 ◽  
Author(s):  
M J Roossinck ◽  
S Jameel ◽  
S H Loukin ◽  
A Siddiqui

We studied the expression of the core region of the hepatitis B virus genome in mammalian cells with recombinant plasmid vectors. Stably transformed rat fibroblast cell lines were established by transfection with vectors containing subgenomic and genome-length hepatitis B virus DNA, followed by G418 selection. The RNA transcripts directed by the core region were characterized by Northern blot hybridization and S1 nuclease mapping. Using the chloramphenicol acetyltransferase gene expression system, the promoter activity located upstream of the core open reading frame was confirmed. The synthesis of core and e polypeptides was studied with a commercial radioimmunoassay. These studies show that partial deletion of the precore sequences abolished secretion of the e antigen, but there was pronounced synthesis of the core antigen in transfected cells.


2008 ◽  
Vol 89 (12) ◽  
pp. 3009-3015 ◽  
Author(s):  
Carla Osiowy ◽  
Diane Gordon ◽  
Jamie Borlang ◽  
Elizabeth Giles ◽  
Jean-Pierre Villeneuve

Hepatitis B virus (HBV) genotype G (HBV/G) is an unusual variant, and little is known about its epidemiology and natural history, particularly the requirement for a co-infecting HBV genotype and their relationship during infection. This study investigated the quasispecies nature of co-infecting genotypes in 39 samples collected over a 6 year period from 13 HBV/G-infected patients. HBV/G infections were found to occur predominantly in males (92 %) and were primarily associated with male homosexual sex (67 %). All patients were infected with HBV/G and HBV/A, or a recombinant HBV/A/G strain. Co-infecting genotypic prevalence was often observed to fluctuate over time, with periods of HBV/G monoinfection in some patients. The average sequence divergence among Canadian HBV/G strains was 1.57±0.62 %. Thus, all HBV/G infections in Canada occur in the context of co-infection or recombination with HBV/A, and strains display increased sequence divergence compared with all known HBV/G sequences described to date.


2009 ◽  
Vol 90 (10) ◽  
pp. 2442-2451 ◽  
Author(s):  
Penelope Garmiri ◽  
André Loua ◽  
Nyankoye Haba ◽  
Daniel Candotti ◽  
Jean-Pierre Allain

The prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) chronic carriage in west Africa is the highest in the world, but its molecular epidemiology remains relatively poorly investigated. Plasma samples from random asymptomatic carriers of HBsAg in Conakry, Guinea, were studied and the complete genome sequences of 81 strains were obtained. Three additional samples from Kumasi, Ghana, were also included in the analysis. Phylogenetic analyses confirmed the dominance of genotype E (95.1 %), including 8.6 % of strains (viral load, 5×103–2.6×108 IU ml−1) comprising dominant variants with large deletions in the core region and minority wild-type variants. The presence of two different patterns of deletions in two and four donors suggested targeted genome fragility between nt 1979 and 2314. The remaining sequences included one subgenotype A3 (1 %) and six A/E recombinant forms (4–7 %). A/E strains with identical points of recombination in three donors suggested strongly that these recombinant HBV strains are circulating and transmitted in the population. Recombination points were concentrated in the core gene. The detection of similar A/E recombinant strains in Ghana suggested a geographical extension of recombinant HBV to the region. The quasispecies of one additional Ghanaian strain sequenced in the pre-surface/surface region resolved into dominant clones of either the A or E genotype, but also three different patterns of A/E recombinant variants. The observation that both deletions of genotype E strains and A/E recombination points are mostly located in the core gene at specific positions indicates a region of the genome where genetic rearrangements preferentially take place.


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