Amino-terminal polypeptides of vimentin are responsible for the changes in nuclear architecture associated with human immunodeficiency virus type 1 protease activity in tissue culture cells

Mol Biol Cell. 2001 Jan;12(1):143-54. doi: 10.1091/mbc.12.1.143.

Abstract

Electron microscopy of human skin fibroblasts syringe-loaded with human immunodeficiency virus type 1 protease (HIV-1 PR) revealed several effects on nuclear architecture. The most dramatic is a change from a spherical nuclear morphology to one with multiple lobes or deep invaginations. The nuclear matrix collapses or remains only as a peripheral rudiment, with individual elements thicker than in control cells. Chromatin organization and distribution is also perturbed. Attempts to identify a major nuclear protein whose cleavage by the protease might be responsible for these alterations were unsuccessful. Similar changes were observed in SW 13 T3 M [vimentin(+)] cells, whereas no changes were observed in SW 13 [vimentin(-)] cells after microinjection of protease. Treatment of SW 13 [vimentin(-)] cells, preinjected with vimentin to establish an intermediate filament network, with HIV-1 PR resulted in alterations in chromatin staining and distribution, but not in nuclear shape. These same changes were produced in SW 13 [vimentin(-)] cells after the injection of a mixture of vimentin peptides, produced by the cleavage of vimentin to completion by HIV-1 PR in vitro. Similar experiments with 16 purified peptides derived from wild-type or mutant vimentin proteins and five synthetic peptides demonstrated that exclusively N-terminal peptides were capable of altering chromatin distribution. Furthermore, two separate regions of the N-terminal head domain are primarily responsible for perturbing nuclear architecture. The ability of HIV-1 to affect nuclear organization via the liberation of vimentin peptides may play an important role in HIV-1-associated cytopathogenesis and carcinogenesis.

MeSH terms

  • Animals
  • Cell Nucleus / drug effects*
  • Cell Nucleus / pathology
  • Cell Nucleus / ultrastructure
  • Cells, Cultured / drug effects
  • Cells, Cultured / ultrastructure
  • Cells, Cultured / virology*
  • Chromatin / drug effects
  • Chromatin / ultrastructure
  • Culture Techniques
  • HIV Protease / metabolism*
  • HIV Protease / pharmacology
  • Humans
  • Mice
  • Microinjections
  • Microscopy, Confocal
  • Peptides / chemical synthesis
  • Peptides / pharmacology
  • Protein Structure, Tertiary
  • Vimentin / chemistry
  • Vimentin / metabolism
  • Vimentin / pharmacology*

Substances

  • Chromatin
  • Peptides
  • Vimentin
  • HIV Protease