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Rous Sarcoma Virus (RSV) and Cancer01:03

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Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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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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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
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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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SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis.

Marisa E McGrath1, Yong Xue2, Carly Dillen1

  • 1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.

Proceedings of the National Academy of Sciences of the United States of America
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SARS-CoV-2 accessory proteins impact disease severity, independent of spike mutations. Non-spike mutations in variants also affect viral replication and pathogenesis, altering clinical presentation.

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Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • The COVID-19 pandemic caused by SARS-CoV-2 continues despite vaccination efforts.
  • Emerging SARS-CoV-2 variants possess mutations, including in spike proteins, that can evade vaccines.
  • Mutations in non-spike genes, particularly accessory genes, may influence viral pathogenesis.

Purpose of the Study:

  • To investigate the role of SARS-CoV-2 accessory protein mutations in pathogenesis.
  • To assess the impact of non-spike mutations on viral replication and disease presentation.
  • To compare the effects of accessory gene deletions and variant spike gene replacements on SARS-CoV-2.

Main Methods:

  • Synthesized SARS-CoV-2 viruses with accessory gene deletions.
  • Created infectious clones with variant spike genes replacing the WA-1 spike.
  • Characterized in vitro and in vivo replication of engineered and variant viruses.

Main Results:

  • Accessory proteins were found to contribute significantly to SARS-CoV-2 pathogenesis.
  • Non-spike mutations were shown to enhance viral replication and host pathogenesis.
  • Mutations in accessory proteins can alter the clinical disease presentation.

Conclusions:

  • SARS-CoV-2 accessory proteins play a crucial role in disease pathogenesis.
  • Non-spike mutations contribute to viral replication and pathogenesis, influencing disease severity.
  • Understanding non-spike mutations is essential for predicting and managing COVID-19 clinical outcomes.