Vimentin inhibits α-tubulin acetylation via enhancing α-TAT1 degradation to suppress the replication of human parainfluenza virus type 3

PLoS Pathog. 2022 Sep 15;18(9):e1010856. doi: 10.1371/journal.ppat.1010856. eCollection 2022 Sep.

Abstract

We previously found that, among human parainfluenza virus type 3 (HPIV3) proteins, the interaction of nucleoprotein (N) and phosphoprotein (P) provides the minimal requirement for the formation of cytoplasmic inclusion bodies (IBs), which are sites of RNA synthesis, and that acetylated α-tubulin enhances IB fusion and viral replication. In this study, using immunoprecipitation and mass spectrometry assays, we determined that vimentin (VIM) specifically interacted with the N-P complex of HPIV3, and that the head domain of VIM was responsible for this interaction, contributing to the inhibition of IB fusion and viral replication. Furthermore, we found that VIM promoted the degradation of α-tubulin acetyltransferase 1 (α-TAT1), through its head region, thereby inhibiting the acetylation of α-tubulin, IB fusion, and viral replication. In addition, we identified a 20-amino-acid peptide derived from the head region of VIM that participated in the interaction with the N-P complex and inhibited viral replication. Our findings suggest that VIM inhibits the formation of HPIV3 IBs by downregulating α-tubulin acetylation via enhancing the degradation of α-TAT1. Our work sheds light on a new mechanism by which VIM suppresses HPIV3 replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Humans
  • Inclusion Bodies, Viral*
  • Nucleoproteins / metabolism
  • Parainfluenza Virus 3, Human* / metabolism
  • Phosphoproteins / metabolism
  • RNA / metabolism
  • Tubulin / metabolism
  • Vimentin / metabolism
  • Virus Replication

Substances

  • Nucleoproteins
  • Phosphoproteins
  • RNA
  • Tubulin
  • Vimentin

Grants and funding

This research was funded by the grants from National Key R&D Program of China(2021YFC2300702 and 2021YFC2300200), the National Natural Science Foundation of China (82130064, 81825015, 31500135, and 81871650), and the Fundamental Research Funds for the Central Universities (2042022kf1188). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.