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

ABSTRACT: 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 influen

SUBMITTER: Sheppard CM 

PROVIDER: S-EPMC10564888 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature