NS1- and minute virus of mice-induced cell cycle arrest: involvement of p53 and p21(cip1)

A Op De Beeck1, J Sobczak-Thepot, H Sirma

  • 1Unité Hépatite C, CNRS-FRE 2369, Institut de Biologie de Lille et Institut Pasteur de Lille, 59021 Lille cedex, France. anne.op-de-beeck@ibl.fr

Journal of Virology
|October 17, 2001
PubMed

Insights

The minute virus of mice (MVMp) nonstructural protein NS1 causes cell cycle arrest by accumulating p21(cip1), while MVMp infection relies on p53 and p21(cip1) for G2 arrest, revealing distinct mechanisms of viral growth inhibition.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • The minute virus of mice (MVMp) nonstructural protein NS1 is cytolytic and induces cell cycle arrest.
  • NS1 expression mimics MVMp infection-induced cell cycle arrest in S and G2 phases.
  • Understanding the molecular mechanisms of NS1 and MVMp-mediated growth inhibition is crucial.

Purpose of the Study:

  • To investigate the molecular mechanisms of cell cycle arrest induced by NS1 and MVMp.
  • To elucidate the roles of p53 and p21(cip1) in MVMp-induced cell cycle regulation.

Main Methods:

  • Analyzing cell cycle arrest in G1, S, and G2 phases upon NS1 expression.
  • Assessing the accumulation of p53 and p21(cip1) in NS1-expressing and MVMp-infected cells.
  • Utilizing p53 wild-type and null cells, as well as p21(cip1) null cells to determine the roles of these proteins.

Main Results:

  • NS1-mediated cell cycle arrest correlates with p21(cip1) accumulation, independent of p53.
  • MVMp infection induces cell cycle arrest in S and G2, dependent on both p53 and p21(cip1).
  • The S phase arrest is p53-dependent but p21(cip1)-independent, while G2 arrest requires both p53 and p21(cip1).

Conclusions:

  • MVMp utilizes distinct pathways for cell cycle arrest during infection versus NS1 expression.
  • p53 is essential for MVMp-induced S phase arrest, while both p53 and p21(cip1) are required for G2 arrest.
  • NS1 induces G2 arrest via p21(cip1) inhibition of cyclin A-dependent kinase activity, suggesting a specific role for NS1 in viral replication.

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