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Related Concept Videos

Viral Mutations00:36

Viral Mutations

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 for adaptive...
Mutations in Microorganisms01:18

Mutations in Microorganisms

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,...
Mutations01:39

Mutations

Overview
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

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...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

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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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
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Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency.

P Richard Harrigan1, Chih-Wei Sheen, Vikram S Gill

  • 1BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada. prharrigan@cfenet.ubc.ca

AIDS (London, England)
|November 14, 2008
PubMed
Summary

Silent mutations in HIV-1 reverse transcriptase (RT) are selected alongside drug resistance mutations. These findings suggest an RNA-level mechanism contributing to HIV therapy resistance.

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Area of Science:

  • Virology
  • Molecular Biology
  • Drug Resistance

Background:

  • Missense mutations in HIV-1 reverse transcriptase (RT) are common under therapy.
  • The role of silent mutations in HIV therapy selection was previously unclear.

Purpose of the Study:

  • To investigate if silent mutations in HIV-1 RT are selected during antiretroviral therapy.
  • To determine the impact of silent mutations on HIV-1 RT function and drug resistance.

Main Methods:

  • Retrospective analysis of HIV-1 RT genes from treatment-naive and experienced individuals.
  • Biochemical assays using purified HIV-1 RT and synthetic RNA/DNA substrates to assess reverse transcription efficiency.

Main Results:

  • Two silent mutations (K65K and K66K) were strongly associated with HIV treatment experience.
  • These silent mutations alleviated pausing and dissociation of HIV-1 RT on RNA templates with drug resistance mutations (D67N, K70R).

Conclusions:

  • Silent mutations at codons 65 and 66 are co-selected with thymidine analogue mutations.
  • This provides the first evidence for an RNA-level mechanism directly impacting HIV drug resistance.