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Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.

ABSTRACT: A hallmark for the development and progression of chronic liver diseases is the persistent dysregulation of signaling pathways related to inflammatory responses, which eventually promotes the development of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The two major etiological agents associated with these complications in immunocompetent patients are hepatitis B virus (HBV) and hepatitis C virus (HCV), accounting for almost 1.4 million liver disease-associated deaths worldwide. Although both differ significantly from the point of their genomes and viral life cycles, they exert not only individual but also common strategies to divert innate antiviral defenses. Multiple virus-modulated pathways implicated in stress and inflammation illustrate how chronic viral hepatitis persistently tweaks host signaling processes with important consequences for liver pathogenesis. The following review aims to summarize the molecular events implicated in the sensing of viral nucleic acids, the mechanisms employed by HBV and HCV to counter these measures and how the dysregulation of these cellular pathways drives the development of chronic liver disease and the progression toward HCC.

SUBMITTER: Roca Suarez AA

PROVIDER: S-EPMC7892431 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.

Roca Suarez Armando Andres AA Testoni Barbara B Baumert Thomas F TF Lupberger Joachim J

Frontiers in immunology 20210205

A hallmark for the development and progression of chronic liver diseases is the persistent dysregulation of signaling pathways related to inflammatory responses, which eventually promotes the development of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The two major etiological agents associated with these complications in immunocompetent patients are hepatitis B virus (HBV) and hepatitis C virus (HCV), accounting for almost 1.4 million liver disease-associated deaths worldwide ...[more]

PMID: 33613561

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Project description:Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification for viral coat proteins making icosahedral virus capsids is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarities, suggesting that the similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds.IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids. Importantly, we detected similarity at the nucleotide level between capsid protein-coding regions from viruses infecting cells belonging to all three domains of life, reproducing a previously established structure-based classification of icosahedral viral capsids.

Dataset Information

Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.

Publications

Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.

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