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Neuraminidase activity modulates cellular co-infection during influenza A virus multicycle growth

Guo, Z.; He, Y.; Benegal, A. N.; Vahey, M. D.

2022-09-20 microbiology
10.1101/2022.09.20.508375 bioRxiv
Show abstract

Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular co-infection during multi-cycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular co-infection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular co-infection. We map this effect to NAs ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases where viral infectious potential is low, genetic or pharmacological inhibition of NA increases the local spread of infection by increasing the viral load received by neighboring cells. These results identify virus-intrinsic factors that contribute to cellular multiplicity of infection, and suggest that optimal levels of NA activity depend on the infectious potential of the virus in question.

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