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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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Viruses with RNA Genomes01:29

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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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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.

Biorxiv : the Preprint Server for Biology
|October 21, 2021
PubMed
Summary
This summary is machine-generated.

SARS-CoV-2 variants show enhanced replication and pathogenesis due to mutations outside the spike gene. These changes in the nucleocapsid protein increase viral RNA and protein levels, aiding adaptation.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Genetic variation in SARS-CoV-2, particularly outside the spike protein, remains understudied.
  • The nucleocapsid (N) protein's highly variable region (residues 203-205) is crucial for viral adaptation.
  • Previous research has primarily focused on spike gene mutations, neglecting other viral components.

Approach:

  • Recreated the R203K+G204R mutation in an early pandemic SARS-CoV-2 strain.
  • Investigated the impact of this mutation on viral replication, fitness, and pathogenesis *in vitro* and *in vivo*.
  • Analyzed the effect of the mutation on nucleocapsid phosphorylation and resistance to GSK-3 kinase inhibition.
  • Created analogous alanine substitutions at positions 203-204 to assess the role of the ancestral 'RG' motif.

Key Points:

  • The R203K+G204R mutation significantly enhances SARS-CoV-2 replication, fitness, and pathogenesis.
  • This mutation leads to increased viral RNA and protein levels, both *in vitro* and *in vivo*.
  • R203K+G204R increases nucleocapsid phosphorylation and confers resistance to GSK-3 kinase inhibition.
  • Disrupting the ancestral 'RG' motif at residues 203-204 enhances viral replication and phosphorylation.

Conclusions:

  • Mutations outside the spike gene, such as those in the nucleocapsid protein, are critical for SARS-CoV-2 adaptation.
  • The R203K+G204R mutation provides a molecular mechanism for enhanced viral replication and pathogenesis.
  • Understanding these non-spike mutations is essential for comprehending SARS-CoV-2 evolution and developing effective countermeasures.