This Week in Virology

TWiV 1307: My heart breaks for flu

Mar 22, 2026
A deep dive into how Rep motors package AAV genomes using cryo-EM, revealing helicase transitions and DNA-threading mechanisms. A separate strand follows influenza hitching a ride in myeloid cells to infect cardiomyocytes and trigger interferon-driven heart damage. Brief news and science picks break up the technical discussions.
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ANECDOTE

Remembering Robin Weiss And His HIV Work

  • Robin Weiss, a respected retrovirologist linked to early HIV receptor work, passed away at 86 and is remembered by Rich Condit for his contributions.
  • Rich noted Weiss's role at the Imperial Cancer Research Fund and seminal observations in HIV biology including CD4 involvement.
INSIGHT

How AAV Rep Motors Package Genomes

  • AAV Rep proteins act as dynamic motors that switch oligomeric states to both melt double-stranded ends and thread single-stranded genomes into capsids.
  • Cryo-EM shows Rep40 forms heptamers on duplex ITRs, donates a subunit to make hexamers, then ATP-driven conformational changes translocate one base per ATP into the capsid.
ADVICE

Use Rep Structures To Improve AAV Yields

  • Improving AAV packaging efficiency is a clear translational goal because current genome insertion into capsids is inefficient and limits gene therapy yields.
  • Structural insight into Rep oligomer transitions and the cryptic ATP site suggests targets for engineering more effective packaging motors.
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