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

• DOI: 10.1038/s41467-023-41308-4
• Publication Date: 2023-10-10T16:02:02Z
• Authors: Carol M. Sheppard; Daniel H. Goldhill; Olivia C. Swann; Ecco Staller; Rebecca Penn; Olivia K. Platt; Ksenia Sukhova; Laury Baillon; Rebecca Frise; Thomas P. Peacock; Ervin Fodor; Wendy S. Barclay
• Keywords: 570; Science; Q; Nuclear Proteins; RNA-Binding Proteins; RNA-Dependent RNA Polymerase; Virus Replication; Nucleotidyltransferases; Article; 3. Good health; Mice; Influenza A virus; Influenza, Human; Humans; Animals; Dimerization; Molecular Chaperones

Abstract Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most viruses cannot replicate in edited human cells lacking both ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an A these unexpectedly, after 2 passages, observe robust viral We find two mutations different subunits of the polymerase that enable mutant to use a novel factor, ANP32E, alternative family member, which is unable support wild type polymerase. Both reside symmetric dimer interface between complexes reduce dimerization. These have previously been identified as adapting mice. Indeed, evolved gains ability suboptimal mouse ANP32 proteins becomes more virulent identify further predict allow adapt through similar mechanism. Overall, our results suggest balance asymmetric dimers influenced by interaction proteins.