CDC25B promotes influenza A virus replication by regulating the phosphorylation of nucleoprotein

Virology. 2018 Dec:525:40-47. doi: 10.1016/j.virol.2018.09.005. Epub 2018 Sep 18.

Abstract

Cell division cycle 25 B (CDC25B) is a member of the CDC25 phosphatase family. It can dephosphorylate cyclin-dependent kinases and regulate the cell division cycle. Moreover, siRNA knockdown of CDC25B impairs influenza A virus (IAV) replication. Here, to further understand the regulatory mechanism of CDC25B for IAV replication, a CDC25B-knockout (KO) 293T cell line was constructed using CRISPR/Cas9. The present data indicated that the replication of IAV was decreased in CDC25B-KO cells. Additionally, CDC25B deficiency damaged viral polymerase activity, nucleoprotein (NP) self-oligomerization, and NP nuclear export. Most importantly, we found that the NP phosphorylation levels were significantly increased in CDC25B-KO cells. These findings indicate that CDC25B facilitates the dephosphorylation of NP, which is vital for regulating NP functions and the life cycle of IAV.

Keywords: CDC25B; Influenza A virus; Nuclear export; Nucleoprotein; Phosphorylation; Self-oligomerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Dogs
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Madin Darby Canine Kidney Cells
  • Nucleoproteins / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / physiology*
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism*

Substances

  • Nucleoproteins
  • Viral Proteins
  • CDC25B protein, human
  • cdc25 Phosphatases