The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis

Benjamin E. Nilsson-Payant, Benjamin R. tenOever, Aartjan J.W. te Velthuis

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Influenza A viruses are negative-sense RNA viruses that rely on their own viral replication machinery to replicate and transcribe their segmented single-stranded RNA genome. The viral ribonucleoprotein complexes in which viral RNA is replicated consist of a nucleoprotein scaffold around which the RNA genome is wound, and a heterotrimeric RNA-dependent RNA polymerase that catalyzes viral replication. The RNA polymerase copies the viral RNA (vRNA) via a replicative intermediate, called the cRNA, and subsequently uses this cRNA to make more vRNA copies. To ensure that new cRNA and vRNA molecules are associated with ribonucleoproteins in which they can be amplified, the active RNA polymerase recruits a second polymerase to encapsidate the cRNA or vRNA. Host factor ANP32A has been shown to be essential for viral replication and to facilitate the formation of a dimer between viral RNA polymerases. Differences between mammalian and avian ANP32A proteins are sufficient to restrict viral replication. It has been proposed that ANP32A is only required for the synthesis of vRNA molecules from cRNA but not vice versa. However, this view does not match recent molecular evidence. Here we use minigenome assays, virus infections, and viral promoter mutations to demonstrate that ANP32A is essential for both vRNA and cRNA synthesis. Moreover, we show that ANP32A is not only needed for the actively replicating polymerase, but not for the polymerase that is encapsidating nascent viral RNA products. Overall, these results provide new insights into influenza A virus replication and host adaptation.

Original languageEnglish (US)
Article numbere02092-21
JournalJournal of virology
Volume96
Issue number4
DOIs
StatePublished - Feb 2022

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Keywords

  • ANP32A
  • Influenza
  • Influenza A virus
  • RNA polymerase
  • RNA polymerases
  • RNA replication
  • Single-molecule FRET

Fingerprint

Dive into the research topics of 'The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis'. Together they form a unique fingerprint.

Cite this