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Area of Science:

  • Immunology
  • Virology
  • Evolutionary Biology

Background:

  • Immunodeficiencies are hypothesized to influence within-host viral evolution.
  • Previous arguments relied on between-host models, leaving the role in primary infections unclear.

Purpose of the Study:

  • To investigate how various immunodeficiencies shape immune responses during primary viral infections.
  • To analyze the impact on viral fitness landscapes and evolutionary rates.

Main Methods:

  • Utilized a mechanistic immunological model.
  • Simulated different immunodeficiency scenarios during primary infection.

Main Results:

  • Neutrophil and interferon deficiencies initially accelerated viral evolution in acute infections, but mutations were less frequent upon clearance.
  • T cell deficiencies slowed evolution in persistent infections, while interleukin-6 and macrophage deficiencies accelerated it.
  • Positive epistatic interactions accelerated the evolution of immune evasion and cell entry mutations.

Conclusions:

  • Immunodeficiencies have complex and varied effects on within-host viral evolution.
  • The interplay between host immunity and viral adaptation is crucial for understanding viral dynamics.