scholarly journals Complete genome sequence of a divergent strain of Tibetan frog hepatitis B virus associated to concave-eared torrent frogOdorrana tormota

2018 ◽  
Author(s):  
Humberto J. Debat ◽  
Terry Fei Fan Ng

AbstractThe familyHepadnaviridaeis characterized by partially dsDNA circular viruses of approximately 3.2 kb, which are reverse transcribed from RNA intermediates. Hepadnaviruses (HBVs) have a broad host range which includes humans (Hepatitis B virus), other mammals (genusOrthohepadnavirus), and birds (Avihepadnavirus). HBVs host specificity has been expanded by reports of new viruses infecting fish, amphibians, and reptiles. The tibetan frog hepatitis B virus (TFHBV) was recently discovered inNanorana parkeri(FamilyDicroglossidae) from Tibet. To increase understanding of hepadnavirus in amphibian host, we identified the full-length genome of a divergent strain TFHBV-Ot associated to the concave-eared torrent frogOdorrana tormota(FamilyRanidae) from China by searching deep sequencing data. TFHBV-Ot shared the genomic organization and a 76.6% overall genome nucleotide identity to the prototype TFHBV associated toN. parkeri(TFHBV-Np). TFHBV-Ot amino acid pairwise identity with TFHBV-Np predicted gene products ranged between 63.9% and 77.9%. Multiple tissue/organ specific RNAseq datasets suggest a broad tropism of TFHBV including muscles, gonads and brains. In addition, we provide for the first time evidence of virus derived small RNA from an amphibian hepadnavirus, tentatively enriched in 19-20 nt species and cytidine as first base. The results presented here expand the genetic diversity and the host range of TFHBV toRanidaefrogs, and warrant investigation on hepadnaviral infection of amphibian brains.

2003 ◽  
Vol 77 (3) ◽  
pp. 1964-1976 ◽  
Author(s):  
Alexej Prassolov ◽  
Heinz Hohenberg ◽  
Tatyana Kalinina ◽  
Carola Schneider ◽  
Lucyna Cova ◽  
...  

ABSTRACT All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.


1991 ◽  
Vol 35 (5) ◽  
pp. 631-637 ◽  
Author(s):  
Ralph Schröder ◽  
Anke Maassen ◽  
Andrea Lippoldt ◽  
Thomas Börner ◽  
Rüdiger von Baehr ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alan J. Mueller-Breckenridge ◽  
Fernando Garcia-Alcalde ◽  
Steffen Wildum ◽  
Saskia L. Smits ◽  
Robert A. de Man ◽  
...  

AbstractChronic infection with Hepatitis B virus (HBV) is a major risk factor for the development of advanced liver disease including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The relative contribution of virological factors to disease progression has not been fully defined and tools aiding the deconvolution of complex patient virus profiles is an unmet clinical need. Variable viral mutant signatures develop within individual patients due to the low-fidelity replication of the viral polymerase creating ‘quasispecies’ populations. Here we present the first comprehensive survey of the diversity of HBV quasispecies through ultra-deep sequencing of the complete HBV genome across two distinct European and Asian patient populations. Seroconversion to the HBV e antigen (HBeAg) represents a critical clinical waymark in infected individuals. Using a machine learning approach, a model was developed to determine the viral variants that accurately classify HBeAg status. Serial surveys of patient quasispecies populations and advanced analytics will facilitate clinical decision support for chronic HBV infection and direct therapeutic strategies through improved patient stratification.


2007 ◽  
Vol 81 (14) ◽  
pp. 7351-7362 ◽  
Author(s):  
Robyn Puro ◽  
Robert J. Schneider

ABSTRACT Tumor necrosis factor (TNF) is critical for the control of hepatitis B virus (HBV) in the clinical setting and in model systems. TNF induces noncytopathic suppression and clearance of HBV in animal models, possibly through reduction of viral nucleocapsids, but the mechanism is not well described. Here, we demonstrate the molecular mechanism and broad host range for TNF action against HBV. We show that TNF rapidly blocks HBV replication by promoting destabilization of preexisting cytoplasmic viral nucleocapsids containing viral RNA and DNA, as well as empty nucleocapsids. TNF destabilized human HBV nucleocapsids in a variety of human hepatocytic cell lines and in primary rat hepatocytes and also destabilized duck HBV (DHBV) nucleocapsids in chicken hepatocytic cells. Lysates from TNF-treated uninfected cells also destabilized HBV nucleocapsids in vitro. Moreover, inhibition of DHBV DNA replication by TNF blocks nuclear accumulation of the viral transcription template, maintenance of which is essential for the establishment and maintenance of chronic infection. We show that TNF destabilization of HBV nucleocapsids does not involve ubiquitination or methylation of the viral core protein and is not mediated by the nitric oxide free radical arm of the TNF pathway. These results define a novel antiviral mechanism mediated by TNF against multiple types of HBVs in different species.


2020 ◽  
Vol 5 ◽  
pp. 240
Author(s):  
Louise O. Downs ◽  
Anna L. McNaughton ◽  
Mariateresa de Cesare ◽  
M. Azim Ansari ◽  
Jacqueline Martin ◽  
...  

Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral diversity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.


2012 ◽  
Vol 93 (9) ◽  
pp. 1899-1907 ◽  
Author(s):  
Bastian Beggel ◽  
Maria Neumann-Fraune ◽  
Matthias Döring ◽  
Glenn Lawyer ◽  
Rolf Kaiser ◽  
...  

The hepatitis B virus (HBV) is classified into distinct genotypes A–H that are characterized by different progression of hepatitis B and sensitivity to interferon treatment. Previous computational genotyping methods are not robust enough regarding HBV dual infections with different genotypes. The correct classification of HBV sequences into the present genotypes is impaired due to multiple ambiguous sequence positions. We present a computational model that is able to identify and genotype inter- and intragenotype dual infections using population-based sequencing data. Model verification on synthetic data showed 100 % accuracy for intergenotype dual infections and 36.4 % sensitivity in intragenotype dual infections. Screening patient sera (n = 241) revealed eight putative cases of intergenotype dual infection (one A–D, six A–G and one D–G) and four putative cases of intragenotype dual infection (one A–A, two D–D and one E–E). Clonal experiments from the original patient material confirmed three out of three of our predictions. The method has been integrated into geno2pheno[hbv], an established web-service in clinical use for analysing HBV sequence data. It offers exact and detailed identification of HBV genotypes in patients with dual infections that helps to optimize antiviral therapy regimens. geno2pheno[hbv] is available under http://www.genafor.org/g2p_hbv/index.php.


2004 ◽  
Vol 78 (10) ◽  
pp. 5233-5243 ◽  
Author(s):  
Azeneth Barrera ◽  
Bernadette Guerra ◽  
Helen Lee ◽  
Robert E. Lanford

ABSTRACT Hepatitis B virus (HBV) and woolly monkey hepatitis B virus (WMHBV) have natural host ranges that are limited to closely related species. The barrier for infection of primates seems to be at the adsorption and/or entry steps of the viral replication cycle, since a human hepatoma cell line is permissive for HBV and WMHBV replication following transfection of cloned DNA. We hypothesized that the HBV and WMHBV envelope proteins contain the principal viral determinants of host range. As previously shown by using the hepatitis D virus (HDV) system, recombinant HBV-HDV particles were infectious in chimpanzee as well as human hepatocytes. We extended the HDV system to include HDV particles pseudotyped with the WMHBV envelope. In agreement with the natural host ranges of HBV and WMHBV, in vitro infections demonstrated that HBV-HDV and WM-HDV particles preferentially infected human and spider monkey cells, respectively. Previous studies have implicated the pre-S1 region of the large (L) envelope protein in receptor binding and host range; therefore, recombinant HDV particles were pseudotyped with the hepadnaviral envelopes containing chimeric L proteins with the first 40 amino acids from the pre-S1 domain exchanged between HBV and WMHBV. Surprisingly, addition of the human amino terminus to the WMHBV L protein increased infectivity on spider monkey hepatocytes but did not increase infectivity for human hepatocytes. Based upon these data, we discuss the possibility that the L protein may be comprised of two domains that affect infectivity and that sequences downstream of residue 40 may influence host range and receptor binding or entry.


2001 ◽  
Vol 75 (23) ◽  
pp. 11565-11572 ◽  
Author(s):  
P. Chouteau ◽  
J. Le Seyec ◽  
I. Cannie ◽  
M. Nassal ◽  
C. Guguen-Guillouzo ◽  
...  

ABSTRACT Infection by hepatitis B virus (HBV) is mainly restricted to humans. This species specificity is likely determined at the early phase of the viral life cycle. Since the envelope proteins are the first viral factors to interact with the cell, they represent attractive candidates for controlling the HBV host range. To investigate this assumption, we took advantage of the recent discovery of a second virus belonging to the primateOrthohepadnavirus genus, the woolly monkey HBV (WMHBV). A recombinant plasmid was constructed for the expression of all WMHBV envelope proteins. In additional constructs, N-terminal sequences of the WMHBV large envelope protein were substituted for their homologous HBV counterparts. All wild-type and chimeric WMHBV surface proteins were properly synthesized by transfected human hepatoma cells, and they were competent to replace the original HBV proteins for the production of complete viral particles. The resulting pseudotyped virions were evaluated for their infectious capacity on human hepatocytes in primary culture. Virions pseudotyped with wild-type WMHBV envelope proteins showed a significant loss of infectivity. By contrast, infectivity was completely restored when the first 30 residues of the large protein originated from HBV. Analysis of smaller substitutions within this domain limited the most important region to a stretch of only nine amino acids. Reciprocally, replacement of this motif by WMHBV residues in the context of the HBV L protein significantly reduced infectivity of HBV. Hence this short region of the L protein contributes to the host range of HBV.


Sign in / Sign up

Export Citation Format

Share Document