Molecular players for forming liquid inclusions in influenza A virus infection

Aidan O'Riain (Universidade Católica Portuguesa & Gulbenkian Institute for Molecular Medicine, Portugal)

14:54 - 15:06 Tuesday 14 April Morning

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Abstract

Influenza A virus (IAV) is a significant human pathogen, causing seasonal flu and occasional pandemics. Recent discoveries show that liquid cytosolic condensates play a relevant role in the IAV infection cycle, potentially at stages such as viral genome trafficking, assembly and packaging. These steps are particularly important as IAV must assemble and package exactly its eight unique genome segments in the jam-packed cytoplasm to produce infectious progeny virions. Interfering with IAV condensate formation or altering condensates material properties reduces virion production, demonstrating their facilitation of the viral replication cycle. However, the mechanism by which IAV condensate formation allows for efficient viral replication remains poorly understood, particularly the contribution of each of the eight viral ribonucleoproteins (vRNPs) to condensate formation. Here, I use a plasmid-based transfection system to investigate the contribution of each individual IAV segment in the formation of viral condensates. With super-resolution microscopy, I show a potential hierarchy in which particular viral segments are increasingly proficient at driving the formation of cytosolic condensates, including some segments which fail to form condensates. Preliminary data shows that condensate formation may be driven by the Matrix 1 (M1) protein, which I have found to be a component of viral inclusions. Such a hierarchy within the context IAV condensates may provide further insight into the cytoplasmic organization of viral segments and their role in specific and efficient viral genome assembly. This work also uncovers M1 as a driving force of IAV condensate formation. Although how exactly, we are yet to fully understand.

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