This Week in Virology

TWiV 1257: Better cocktails and CRISPR chicken

Sep 28, 2025
Explore groundbreaking experiments creating genetically modified chickens that resist avian influenza using CRISPR technology. The hosts discuss how these edits impact viral shedding and the risks of viral escape mutations. Transitioning to HTLV-1, they unveil innovative therapies that show promise in eradicating the virus in humanized mice. The risks and history of emerging pathogens meet the excitement of scientific advancement in this engaging and informative discussion.
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INSIGHT

ANP32 Dependency Controls Avian Flu Replication

  • Avian influenza polymerase depends on host ANP32 proteins, and avian ANP32 variants enable efficient viral replication.
  • Editing chicken ANP32A can block polymerase activity and reduce viral shedding and transmission in vivo.
INSIGHT

Two Amino Acids Can Dramatically Reduce Shedding

  • Introducing two amino acid substitutions into chicken ANP32A abolished avian polymerase activity in mini-genome assays.
  • Genetically edited chickens showed no detectable virus shedding in most birds and prevented sentinel transmission at standard inocula.
INSIGHT

Escape Mutations Undercut Single-Gene Edits

  • High-dose challenge selected viral polymerase mutations that restored activity despite ANP32A edits.
  • Viral escape mutations (e.g., E349K in PA) can overcome single-gene host edits by altering polymerase interfaces.
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