TWiV 1307: My heart breaks for flu

This Week in Virology episode 1307 dives into two groundbreaking papers that illuminate the hidden mechanisms of viral infection and immune response. The first paper, published in Cell Reports, reveals the intricate structural mechanics of adeno-associated virus (AAV) DNA packaging, showcasing how the Rep40 protein acts as a molecular motor to pump single-stranded DNA into viral capsids using ATP hydrolysis. The study, using cryo-electron microscopy, uncovers a dynamic process where a heptamer of Rep40 docks onto a pentamer bound to the capsid, triggering a subunit shuffle that melts double-stranded DNA and initiates packaging—highlighting the remarkable efficiency of this minimalistic virus. The second paper, in Immunity, uncovers a surprising pathway by which influenza virus causes heart damage: it hijacks myeloid cells (specifically pro-DC3s) to ferry the virus to cardiomyocytes in the heart. Once there, viral replication triggers a damaging type I interferon response, not the virus itself, which explains why antivirals are ineffective once symptoms appear. The heart damage is due to interferon signaling in cardiomyocytes, not direct infection, suggesting a new therapeutic target. The episode also features updates on the ASV 2026 conference, a tribute to virologist Robin Weiss, a legal challenge to RFK Jr.'s vaccine policies, and personal reflections on science, vaccines, and the mind-bending nature of biology and physics. The hosts emphasize the importance of vaccination, scientific rigor, and the wonder of molecular mechanisms.