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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...
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
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...
Gene Evolution - Fast or Slow?02:05

Gene Evolution - Fast or Slow?

The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...

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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses

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Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolution.

Bin Li1, Adrianne D Gladden, Marcus Altfeld

  • 1Partners AIDS Research Center, MGH-East, CNY 6616, 149 13th Street, Charlestown, MA 02129, USA.

Journal of Virology
|October 27, 2006
PubMed
Summary

Human immunodeficiency virus type 1 (HIV-1) mutations often revert to ancestral forms, limiting viral adaptation to immune pressure. This suggests HIV-1 may not continuously evolve against host defenses, preserving vaccine targets.

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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses

Published on: May 4, 2015

Area of Science:

  • Virology
  • Immunology
  • Evolutionary Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) replication is error-prone, allowing immune evasion.
  • CD8+ T-cell escape mutations are observed, suggesting viral adaptation to host immunity.
  • Some escape mutations revert upon transmission, restoring viral replication capacity.

Purpose of the Study:

  • To investigate the role of reversions in early HIV-1 evolution.
  • To analyze sequence polymorphisms and their reversion rates in primary HIV-1 infection.

Main Methods:

  • Longitudinal sequencing of HIV-1 genomes from seven subjects up to 1 year post-primary infection.
  • Analysis of sequence polymorphisms, particularly within CD8+ T-cell epitopes.
  • Comparison of reversion rates versus forward mutation rates.

Main Results:

  • Numerous nonsynonymous mutations were found within CD8+ T-cell epitopes, confirming immune pressure.
  • A significant proportion (42%) of substitutions reverted to the clade B consensus sequence.
  • Reversions occurred significantly faster than forward mutations, especially in structurally conserved residues.

Conclusions:

  • Many transmitted HIV-1 mutations incur a fitness cost, which is recovered by reverting to an optimal ancestral form.
  • The propensity for mutation reversion may limit the accumulation of immune-driven mutations in the HIV-1 population.
  • Reversion dynamics suggest HIV-1 adaptation is not unremitting, potentially preserving epitopes for vaccine development.