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Related Concept Videos

Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Mutations in Microorganisms01:18

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Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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Size and Structure of Viral Genomes01:26

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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Genome Copying Errors02:46

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DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Updated: Sep 7, 2025

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
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Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis.

Bryan A Johnson1, Yiyang Zhou2, Kumari G Lokugamage1

  • 1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Plos Pathogens
|June 21, 2022
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Summary
This summary is machine-generated.

Mutations in the SARS-CoV-2 nucleocapsid protein, outside the spike gene, enhance viral replication and pathogenesis. These changes increase viral RNA and protein levels, aiding virus adaptation.

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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Genetic variation in SARS-CoV-2 is crucial for its adaptation.
  • Focus has been on spike gene mutations, leaving other regions unexplored.
  • The nucleocapsid protein's variable region (residues 203-205) is implicated in viral evolution.

Purpose of the Study:

  • To investigate the role of mutations in the SARS-CoV-2 nucleocapsid protein (N protein) at residues 203-205.
  • To determine if mutations found in variants like Alpha and Omicron enhance viral replication and pathogenesis.
  • To elucidate the molecular mechanisms underlying enhanced viral fitness.

Main Methods:

  • Recreating the R203K+G204R mutation in an early pandemic SARS-CoV-2 strain (WA-1).
  • Assessing viral replication, fitness, and pathogenesis in vitro and in vivo.
  • Measuring viral RNA and protein levels.
  • Analyzing nucleocapsid protein phosphorylation and its interaction with GSK-3 kinase.

Main Results:

  • The R203K+G204R mutation significantly enhanced SARS-CoV-2 replication, fitness, and pathogenesis.
  • Mutant viruses showed increased viral RNA and protein levels.
  • Increased nucleocapsid phosphorylation and resistance to GSK-3 kinase inhibition were observed.
  • Ablation of the ancestral 'RG' motif at residues 203-204 enhanced replication and phosphorylation.

Conclusions:

  • Genetic variations outside the spike gene, specifically in the nucleocapsid protein, are critical for SARS-CoV-2 adaptation.
  • The R203K+G204R mutation provides a molecular basis for increased viral replication and pathogenesis.
  • Targeting non-spike mutations offers new avenues for understanding and controlling SARS-CoV-2 evolution.