Hepatitis B virus X protein blocks filamentous actin bundles by interaction with eukaryotic translation elongat ion factor 1 alpha 1

Lin, Wei; Jiao, Bo-Yan; Wu, Yunli; Chen, Wan-Nan; Lin, Xu

doi:10.1002/jmv.23283

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…This further adds to the substantial evidence for an oncogenic effect of the X gene of orthohepadnaviruses [21] , [22] , [23] , [24] , [25] , [26] . Although the X protein is known to have several indispensable functions in regulation of protein interactions [26] , [67] , [68] , the initial selective advantage during its de-novo emergence remains enigmatic in the light of the otherwise highly stable, streamlined genomes of Hepadnaviridae.…”

Section: Discussionmentioning

confidence: 99%

Early Mesozoic Coexistence of Amniotes and Hepadnaviridae

et al. 2014

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Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic “fossil” is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote–HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

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Section: Discussionmentioning

confidence: 99%

Early Mesozoic Coexistence of Amniotes and Hepadnaviridae

et al. 2014

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“…Despite their genomic similarities, the most striking difference between Orthohepadnaviridae and Avihepadnaviridae is the presence of an X protein in the genomes of human and other mammalian HBVs 8 , a regulatory protein with multiple proteininteracting functions [18][19][20] and a tumor-promoting effect 18 . When we thus performed tBLASTn searches of mammalian HBV X proteins in the eZHBV_C genome, we found no evidence for the presence of an intact or at least a degenerated X ORF in this Mesozoic paleovirus.…”

Section: Resultsmentioning

confidence: 99%

The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses

et al. 2013

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Paleovirology involves the identification of ancient endogenous viral elements within eukaryotic genomes. The evolutionary origins of the reverse-transcribing hepatitis B viruses, however, remain elusive, due to the small number of endogenized sequences present in host genomes. Here we report a comprehensively dated genomic record of hepatitis B virus endogenizations that spans bird evolution from 482 to o12.1 million years ago. The oldest virus relic extends over a 99% complete hepatitis B virus genome sequence and constitutes the first discovery of a Mesozoic paleovirus genome. We show that Hepadnaviridae are 463 million years older than previously known and provide direct evidence for coexistence of hepatitis B viruses and birds during the Mesozoic and Cenozoic Eras. Finally, phylogenetic analyses and distribution of hepatitis B virus relics suggest that birds potentially are the ancestral hosts of Hepadnaviridae and mammalian hepatitis B viruses probably emerged after a bird-mammal host switch. Our study reveals previously undiscovered and multi-faceted insights into prehistoric hepatitis B virus evolution and provides valuable resources for future studies, such as in-vitro resurrection of Mesozoic hepadnaviruses.

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“…Protein-protein interaction network (Figure 5) showed several significant proteins might function in response to HBV, such as actins (ACTA2, ACTB, ACTBL2, ACTN3, and ACTN4), apolipoproteins (APOA2, APOA5, APOB, APOC3, and APOC4), heat shock proteins (HSP90AA1 and HSP90AB1), and proteasome subunit proteins (PSMA1 and PSMA4). It has been reported that HBV core proteins can interact with the C-terminal region of actin-binding protein [60] and HBV X protein (HBx) can block filamentous actin bundles by interaction with eEF1A1 (eukaryotic translation elongation factor 1 alpha 1) [61]. In addition, ACTA2 is a marker of hepatitis stellate cells and correlated significantly with necroinflammatory grades and fibrotic stages in CHB or CHC [13].…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine

Yang

et al. 2016

BioMed Research International

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Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig) related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin), PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin), ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.

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Hepatitis B virus X protein blocks filamentous actin bundles by interaction with eukaryotic translation elongat ion factor 1 alpha 1

Cited by 11 publications

References 29 publications

Early Mesozoic Coexistence of Amniotes and Hepadnaviridae

Early Mesozoic Coexistence of Amniotes and Hepadnaviridae

The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses

iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine

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