Invitée équipe S. Longhi: Maria João Amorim, Instituto Gulbenkian de Ciência, Oeiras, Portugal – “New opportunities to combat influenza A virus infection”

Résumé

Many viruses form biomolecular condensates de novo as part of their replication programmes. Influenza A virus is an important human pathogen that has a genome divided into eight different RNA segments. Interestingly, each infectious particle contains no more than eight RNA segments and one of each type. Here, we show that during infection influenza forms liquid condensates named viral inclusions where the eight RNA segments accumulate. Viral inclusions are formed with a single RNA type, suggesting that these structures are formed before the genomic complex assembles and raises the hypothesis that these are specialized sites for the formation of influenza epidemic and pandemic genomic complexes. We will exchange views on why being liquid could constitute an interesting framework for understanding how influenza genomic complex forms. After, we will expose advances on how viral inclusions are formed and provide proof of the concept that condensate hardening blocks viral infection in cellula and in vivo. Since native or engineered transitions affect condensate behavior, phase transitions may offer novel antiviral opportunities for influenza, as well as for many other viruses that utilize biomolecular condensates during their lifecycle. Finally, we will show that our efforts to reconstitute in vitro influenza A virus inclusions give rise a network of interactions built specifically during infection that phase separates but despite being dynamic are not liquid but rather a gel-like state. We debate several hypothesis on why we have been unable for far to attain a liquid-like character.