scholarly journals The role of mutational robustness in RNA virus evolution

2013 ◽  
Vol 11 (5) ◽  
pp. 327-336 ◽  
Author(s):  
Adam S. Lauring ◽  
Judith Frydman ◽  
Raul Andino
Keyword(s):  
Rna Virus ◽  
Virus Evolution ◽  
Mutational Robustness

Biophysical determinants of mutational robustness in a viral molecular fitness landscape

2017 ◽  
Author(s):  
Manasi A. Pethe ◽  
Aliza B. Rubenstein ◽  
Dmitri Zorine ◽  
Sagar D. Khare
Keyword(s):  
Fitness Landscape ◽  
Rna Virus ◽  
Fitness Landscapes ◽  
Viral Fitness ◽  
Mutational Robustness ◽  
Hcv Protease ◽  
Viral Polyprotein ◽  
Biophysical Interactions ◽  
Proteins And Peptides

Biophysical interactions between proteins and peptides are key determinants of genotype-fitness landscapes, but an understanding of how molecular structure and residue-level energetics at protein-peptide interfaces shape functional landscapes remains elusive. Combining information from yeast-based library screening, next-generation sequencing and structure-based modeling, we report comprehensive sequence-energetics-function mapping of the specificity landscape of the Hepatitis C Virus (HCV) NS3/4A protease, whose function — site-specific cleavages of the viral polyprotein — is a key determinant of viral fitness. We elucidate the cleavability of 3.2 million substrate variants by the HCV protease and find extensive clustering of cleavable and uncleavable motifs in sequence space indicating mutational robustness, and thereby providing a plausible molecular mechanism to buffer the effects of low replicative fidelity of this RNA virus. Specificity landscapes of known drug-resistant variants are similarly clustered. Our results highlight the key and constraining role of molecular-level energetics in shaping plateau-like fitness landscapes from quasispecies theory.

scholarly journals Codon Usage Determines the Mutational Robustness, Evolutionary Capacity, and Virulence of an RNA Virus

2012 ◽  
Vol 12 (5) ◽  
pp. 623-632 ◽  
Author(s):  
Adam S. Lauring ◽  
Ashley Acevedo ◽  
Samantha B. Cooper ◽  
Raul Andino
Keyword(s):  
Codon Usage ◽  
Rna Virus ◽  
Mutational Robustness

scholarly journals Essential role of IPS-1 in innate immune responses against RNA viruses

2006 ◽  
Vol 203 (7) ◽  
pp. 1795-1803 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Hiroki Kato ◽  
Shintaro Sato ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

scholarly journals Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

2020 ◽  
Vol 22 (1) ◽  
pp. 323
Author(s):  
Ramesh Kumar ◽  
Divya Mehta ◽  
Nimisha Mishra ◽  
Debasis Nayak ◽  
Sujatha Sunil
Keyword(s):  
Rna Virus ◽  
Viral Proteins ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Viral Protein Synthesis ◽  
Post Translational Modifications ◽  
Small Proteins ◽  
Cellular Machinery ◽  
Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

scholarly journals Role of Sindbis Virus Capsid Protein Region II in Nucleocapsid Core Assembly and Encapsidation of Genomic RNA

2008 ◽  
Vol 82 (9) ◽  
pp. 4461-4470 ◽  
Author(s):  
Ranjit Warrier ◽  
Benjamin R. Linger ◽  
Barbara L. Golden ◽  
Richard J. Kuhn
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Sindbis Virus ◽  
Rna Virus ◽  
Genomic Rna ◽  
Viral Glycoproteins ◽  
Infected Cells ◽  
Viral Genomic Rna ◽  
Region Ii

ABSTRACT Sindbis virus is an enveloped positive-sense RNA virus in the alphavirus genus. The nucleocapsid core contains the genomic RNA surrounded by 240 copies of a single capsid protein. The capsid protein is multifunctional, and its roles include acting as a protease, controlling the specificity of RNA that is encapsidated into nucleocapsid cores, and interacting with viral glycoproteins to promote the budding of mature virus and the release of the genomic RNA into the newly infected cell. The region comprising amino acids 81 to 113 was previously implicated in two processes, the encapsidation of the viral genomic RNA and the stable accumulation of nucleocapsid cores in the cytoplasm of infected cells. In the present study, specific amino acids within this region responsible for the encapsidation of the genomic RNA have been identified. The region that is responsible for nucleocapsid core accumulation has considerable overlap with the region that controls encapsidation specificity.

scholarly journals RNA-Protein Interaction Analysis of SARS-CoV-2 5′ and 3′ Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection

mSystems ◽  
2021 ◽  
Author(s):  
Rohit Verma ◽  
Sandhini Saha ◽  
Shiv Kumar ◽  
Shailendra Mani ◽  
Tushar Kanti Maiti ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Rna Virus ◽  
Untranslated Regions ◽  
Host Proteins ◽  
Positive Strand ◽  
Replication Complex ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna ◽  
Viral Genomic Rna

Replication of a positive-strand RNA virus involves an RNA-protein complex consisting of viral genomic RNA, host RNA(s), virus-encoded proteins, and host proteins. Dissecting out individual components of the replication complex will help decode the mechanism of viral replication. 5′ and 3′ UTRs in positive-strand RNA viruses play essential regulatory roles in virus replication.

scholarly journals Formation of plant RNA virus replication complexes on membranes: role of an endoplasmic reticulum-targeted viral protein

1997 ◽  
Vol 16 (13) ◽  
pp. 4049-4059 ◽  
Author(s):  
Mary C. Schaad ◽  
Patricia E. Jensen ◽  
James C. Carrington
Keyword(s):  
Endoplasmic Reticulum ◽  
Virus Replication ◽  
Viral Protein ◽  
Rna Virus

scholarly journals A61 Large RNA genomes: Is RNA polymerase fidelity enough?

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
F Ferron ◽  
B Canard
Keyword(s):  
Rna Polymerase ◽  
Rna Synthesis ◽  
Rna Virus ◽  
Virus Genome ◽  
Gene Products ◽  
Dna Viruses ◽  
Viral Rdrp ◽  
Polymerase Fidelity ◽  
Mechanistic Basis

Abstract Large-genome Nidoviruses and Nidovirus-like viruses reside at the current boundary of largest RNA genome sizes. They code for an unusually large number of gene products matching that of small DNA viruses (e.g. DNA bacteriophages). The order of appearance and distribution of enzyme genes along various virus families (e.g. helicase and ExoN) may be seen as an evolutionary marker in these large RNA genomes lying at the genome size boundary. A positive correlation exists between (+)RNA virus genome sizes and the presence of the RNA helicase and the ExoN domains. Although the mechanistic basis of the presence of the helicase is still unclear, the role of the ExoN activity has been linked to the existence of an RNA synthesis proofreading system. In large Nidovirales, ExoN is bound to a processive replicative RNA-dependent RNA polymerase (RdRp) and corrects mismatched bases during viral RNA synthesis. Over the last decade, a view of the overall process has been refined in Coronaviruses, and in particular in our lab (Ferron et al., PNAS, 2018). We have identified genetic markers of large RNA genomes that we wish to use to data-mine currently existing metagenomic datasets. We have also initiated a collaboration to sequence and explore new viromes that will be searched according to these criteria. Likewise, we have a collection of purified viral RdRps that are currently being used to generate RNA synthesis products that will be compared to existing NGS datasets of cognate viruses. We will be able to have an idea about how much genetic diversity is possibly achievable by viral RdRp (‘tunable fidelity’) versus the detectable diversity (i.e. after selection in the infected cell) that is actually produced.

scholarly journals Regulation of positive-strand RNA virus replication: The emerging role of phosphorylation

2007 ◽  
Vol 129 (2) ◽  
pp. 73-79 ◽  
Author(s):  
Anna Jakubiec ◽  
Isabelle Jupin
Keyword(s):  
Virus Replication ◽  
Rna Virus ◽  
Positive Strand ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna
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