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Human defensins drive viral evolution by selecting for mutations in viruses like adenovirus, altering their infection capabilities and transmission. This research reveals how innate immunity shapes pathogen adaptability.

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Area of Science:

  • Immunology
  • Virology
  • Evolutionary Biology

Background:

  • Enteric alpha-defensins are key innate immunity components in the small intestine.
  • Some enteric microbes resist or exploit defensins for infection, suggesting selective pressure.
  • Adenoviruses, common pathogens, interact with host immune factors.

Purpose of the Study:

  • To investigate if defensins impose selective pressure on viruses during fecal-oral transmission.
  • To understand the molecular mechanisms of defensin-virus interactions and their evolutionary impact.

Main Methods:

  • Passaging a defensin-sensitive adenovirus serotype in the presence of human defensins.
  • Analyzing mutations in viral capsid proteins, particularly hexon.
  • Conducting infection and biochemical assays to assess viral infectivity and intracellular trafficking.

Main Results:

  • Mutations accumulated in the adenovirus major capsid protein hexon when passaged with human defensins.
  • Defensin interactions with multiple capsid proteins, not just vertex proteins, influence infection.
  • A balance between enhanced cell binding and impaired intracellular trafficking, mediated by defensin interactions, determines infection outcome.

Conclusions:

  • Defensins exert selective pressure on viral evolution, driving changes in capsid proteins.
  • These interactions revise the understanding of defensin-antiviral mechanisms against non-enveloped viruses.
  • Defensins likely shape viral evolution, leading to varied infection phenotypes in related viruses.