An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization.

Autor: Sheppard, Carol M., Goldhill, Daniel H., Swann, Olivia C., Staller, Ecco, Penn, Rebecca, Platt, Olivia K., Sukhova, Ksenia, Baillon, Laury, Frise, Rebecca, Peacock, Thomas P., Fodor, Ervin, Barclay, Wendy S.
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Zdroj: Nature Communications; 10/10/2023, Vol. 14 Issue 1, p1-16, 16p
Abstrakt: Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth. We find two mutations in different subunits of the influenza polymerase that enable the mutant virus to use a novel host factor, ANP32E, an alternative family member, which is unable to support the wild type polymerase. Both mutations reside in the symmetric dimer interface between two polymerase complexes and reduce polymerase dimerization. These mutations have previously been identified as adapting influenza viruses to mice. Indeed, the evolved virus gains the ability to use suboptimal mouse ANP32 proteins and becomes more virulent in mice. We identify further mutations in the symmetric dimer interface which we predict allow influenza to adapt to use suboptimal ANP32 proteins through a similar mechanism. Overall, our results suggest a balance between asymmetric and symmetric dimers of influenza virus polymerase that is influenced by the interaction between polymerase and ANP32 host proteins. Despite their essentiality, human ANP32A and ANP32B are redundant host factors for influenza virus genome replication. In this work, authors show that an influenza virus grown in cells lacking ANP32A and ANP32B evolved to use ANP32E. They explore the polymerase mutations that enable this, and demonstrate increased virulence in mice. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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