The Major Capsid Protein, VP1, of the Mouse Polyomavirus Stimulates the Activity of Tubulin Acetyltransferase 1 by Microtubule Stabilization

Viruses. 2020 Feb 18;12(2):227. doi: 10.3390/v12020227.


Viruses have evolved mechanisms to manipulate microtubules (MTs) for the efficient realization of their replication programs. Studying the mechanisms of replication of mouse polyomavirus (MPyV), we observed previously that in the late phase of infection, a considerable amount of the main structural protein, VP1, remains in the cytoplasm associated with hyperacetylated microtubules. VP1-microtubule interactions resulted in blocking the cell cycle in the G2/M phase. We are interested in the mechanism leading to microtubule hyperacetylation and stabilization and the roles of tubulin acetyltransferase 1 (αTAT1) and deacetylase histone deacetylase 6 (HDAC6) and VP1 in this mechanism. Therefore, HDAC6 inhibition assays, αTAT1 knock out cell infections, in situ cell fractionation, and confocal and TIRF microscopy were used. The experiments revealed that the direct interaction of isolated microtubules and VP1 results in MT stabilization and a restriction of their dynamics. VP1 leads to an increase in polymerized tubulin in cells, thus favoring αTAT1 activity. The acetylation status of MTs did not affect MPyV infection. However, the stabilization of MTs by VP1 in the late phase of infection may compensate for the previously described cytoskeleton destabilization by MPyV early gene products and is important for the observed inhibition of the G2→M transition of infected cells to prolong the S phase.

Keywords: VP1; histone deacetylase 6; microtubule acetylation; microtubule stabilization; microtubules; mouse polyomavirus; α-tubulin acetyltransferase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Animals
  • Capsid Proteins / genetics*
  • Capsid Proteins / metabolism
  • Cell Cycle
  • Cell Line
  • Cytoplasm / metabolism
  • Fibroblasts / virology
  • Histone Deacetylase 6 / genetics
  • Histone Deacetylase 6 / metabolism
  • Host Microbial Interactions*
  • Mice
  • Microtubules / metabolism*
  • Microtubules / virology
  • Polyomavirus / genetics
  • Polyomavirus / metabolism*
  • Protein Processing, Post-Translational
  • Tubulin / metabolism


  • Capsid Proteins
  • Tubulin
  • VP1 protein, polyomavirus
  • Acetyltransferases
  • Hdac6 protein, mouse
  • Histone Deacetylase 6