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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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Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

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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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Viral Recombination00:57

Viral Recombination

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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.
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Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

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The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
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Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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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...
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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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Constrained Evolutionary Funnels Shape Viral Immune Escape.

Marian Huot1,2, Dianzhuo Wang2,3, Eugene Shakhnovich2

  • 1Laboratory of Physics of the École Normale Supérieure, CNRS UMR 8023 and PSL Research, Sorbonne Université, 24 rue Lhomond, Paris, France.

Biorxiv : the Preprint Server for Biology
|November 24, 2025
PubMed
Summary
This summary is machine-generated.

Predicting viral escape from antibodies is key to understanding variant evolution. A new framework reveals immune evasion follows limited, viable paths due to protein structure and antibody constraints, slowing adaptation.

Keywords:
Antibody escapeMutational pathwaysProtein evolutionRestricted Boltzmann machinesSARS-CoV-2Viral adaptation

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Area of Science:

  • Virology
  • Structural Biology
  • Evolutionary Biology

Background:

  • Viral evolution under immune pressure drives the emergence of antibody-resistant variants.
  • Understanding the constraints on viral adaptation is crucial for predicting future outbreaks.

Purpose of the Study:

  • To develop a probabilistic framework for predicting viral evolutionary trajectories under immune pressure.
  • To identify the key constraints (protein viability and antibody escape) shaping viral adaptation pathways.

Main Methods:

  • Utilized a generative model trained on structural homologs and deep mutational scanning data.
  • Developed a mean-field approximation to analyze evolutionary path ensembles.
  • Applied the framework to the SARS-CoV-2 receptor binding domain.

Main Results:

  • Immune evasion is funneled through a limited number of viable evolutionary paths.
  • The framework accurately predicts mutation sites in SARS-CoV-2 variants of concern.
  • Antibody combinations with de-correlated escape profiles significantly slow viral adaptation.

Conclusions:

  • Viral adaptation is constrained by protein structural viability and antibody escape mechanisms.
  • Predictive modeling of evolutionary trajectories can anticipate variant emergence.
  • Strategic antibody cocktail design can enhance therapeutic efficacy against viral evolution.