Biology

Dr. Indranil Banerjee
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

Viruses are masters of camouflage and deception, despite being extremely simple in structure and composition. Devoid of any means of independent locomotion, they disseminate by exploiting cells and organisms. A critical moment comes when a virus particle reaches a potential host cell and attaches itself to the surface -- it must now deliver its genome and accessory proteins into the host cell for replication. Unable to gain access to cell interior on their own, viruses have evolved elegant strategies to extract assistance form the host cell for their entry and genome release. Recently we have found that influenza virus, one of the most devastating human pathogens, uses a unique trick to get its capsid unpacked and genome released within the host cell by hijacking some important cellular components.  Craftily, it mimics misfolded protein aggregates by carrying unanchored ubiquitin chains, and thereby, activates the ubiquitin- and HDAC6-dependent protein degradation machinery (aggresome) of the cell. Upon activation, diverse components of the aggresome processing machinery including the microtubule- and actin-associated molecular motors dynein, dynactin, and myosin 10, generate physical forces by ‘tug and pull’ to crack open the viral capsid, and release the viral RNA genome into the cytosol for replication. This cytoskeleton motor-assisted capsid disassembly program not only provides yet another interesting insight on how viruses manipulate the host cells to propagate, but also offers potential targets such as HDAC6 for developing novel antiviral strategies to combat this deadly virus.