Evidence for Positive Epistasis in HIV-1

  title={Evidence for Positive Epistasis in HIV-1},
  author={Sebastian Bonhoeffer and Colombe Chappey and Neil T Parkin and Jeanette M Whitcomb and Christos J. Petropoulos},
  pages={1547 - 1550}
Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a… 

Epistasis in RNA Viruses

Two new studies of RNA viruses are discussed and two new theories suggested that recombination has been favored by selection because of the nature of epistatic interactions are discussed.

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

A thorough analysis of a classical AZT-resistance pathway of HIV-1 variants by fitness measurements in single round infection assays covering physiological drug concentrations ex vivo suggests that epistasis might be inefficient as a buffering mechanism for fitness losses in vivo.

Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease

The results support the view that strong compensatory effects are involved in the emergence of clinically observed resistance mutations and provide insights to understanding fitness barriers in the evolution and reversion of drug resistance.

Sexual reproduction selects for robustness and negative epistasis in artificial gene networks

Using an artificial gene network model, this work finds that recombination between gene networks imposes selection for genetic robustness, and that negative epistasis evolves as a by-product of this selection.

Epistasis as a Determinant of the HIV-1 Protease's Robustness to Mutation

Strong and widespread epistatic interactions were observed when the effect of the same mutation was compared in both proteases, suggesting that epistasis can be a key determinant of the robustness displayed by the in vitro generated protease.

Modeling HIV infection dynamics: the role of recombination in the development of drug resistance

The benefit of recombination to HIV remains unclear because just as recombination can induce the association of favorable mutations and accelerate the development of multidrug resistance, it can also

The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV- 1 eradication.

Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus

A simple model is developed in which the phenotypic effects of mutations are completely additive and epistatic interactions arise as a result of the form of the phenotype-to-fitness mapping, which provided a good explanation for the data and the observed patterns of epistatic interaction.

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

Investigating fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein found to be common and complex, involving not only pairwise interactions, but also higher-order interactions.




This work examines two components of fitness, both of which are thought to be important in natural populations of parasitic wasps: longevity and egg production, and shows synergistic epistasis for longevity, but not for egg production.

Patterns of epistasis in RNA viruses: a review of the evidence from vaccine design

It is indicated that no consistent tendency towards a particular form of epistasis exists across RNA viruses and significant interactions among groups of mutations within individual viruses occur but are not common.

Little Evidence for Synergism Among Deleterious Mutations in a Nonsegmented RNA Virus

  • S. Elena
  • Biology
    Journal of Molecular Evolution
  • 1999
Evidence is presented that deleterious mutations in foot-and-mouth disease virus produce a decline in fitness but that the relationship between the number of mutations fixed and the magnitude of fitness decline is compatible mainly with a nonsynergistic model.

The contribution of epistasis to the architecture of fitness in an RNA virus.

The results show that the architecture of the fitness depends on complex interactions among genome components, including antagonistic and synergistic epistasis.

Test of synergistic interactions among deleterious mutations in bacteria

The mutational deterministic hypothesis for the evolution of sex is not supported, because several pairs exhibit significant interactions for fitness, but they are antagonistic as often as they are synergistic.

Recombination: Multiply infected spleen cells in HIV patients

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Epistasis and Its Relationship to Canalization in the RNA Virus φ6

Evidence that positive epistasis is characteristic of deleterious mutations in the RNA bacteriophage φ6 is provided and the results suggest that even random mutations impact the degree of canalization, the buffering of a phenotype against genetic and environmental perturbations.

Dynamics of HIV-1 recombination in its natural target cells

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Why sex and recombination?

The effect of sex and recombination in breaking down negative correlations between favorable variants at different genetic loci, which increases the efficiency of natural selection, is likely to be a major factor favoring their evolution and maintenance.

Recombination in HIV and the evolution of drug resistance: for better or for worse?

A population genetic model of HIV replication is developed that incorporates the processes of mutation, cellular superinfection, and recombination and finds that recombination is expected to slow down the rate of evolution of multi-drug-resistant virus during therapy.