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Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP

Kartika Padhan1, Rinki Minakshi1, Mohammad Aatif Bin Towheed1

  • 1Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India.

The Journal of General Virology
|July 18, 2008
PubMed

Insights

Severe acute respiratory syndrome coronavirus 3a protein induces apoptosis by modulating the mitochondrial death pathway. This involves p38 MAPK activation and affects caspase and p53 pathways, leading to programmed cell death.

Area of Science:

  • Molecular biology
  • Virology
  • Cellular pathology

Background:

  • Severe acute respiratory syndrome coronavirus (SARS-CoV) infection causes significant pathology, but its molecular mechanisms remain unclear.
  • Viral proteins, such as SARS-CoV 3a protein, are implicated in inducing apoptosis (programmed cell death).
  • The specific cellular targets and pathways affected by the 3a protein in apoptosis induction require further characterization.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which the SARS-CoV 3a protein induces apoptosis.
  • To identify the cellular pathways and targets modulated by the 3a protein during viral infection.
  • To present a model for 3a protein-mediated apoptosis.

Main Methods:

  • Analysis of the mitochondrial death pathway in cells expressing the 3a protein.
  • Investigating the roles of caspases (caspase-8, caspase-9), Bid, cytochrome c, Bax, and p53.
  • Assessing the involvement of p38 MAP kinase (MAPK) and STAT3.
  • Utilizing p38 MAPK inhibitors (SB203580) and Annexin V staining.

Main Results:

  • The 3a protein modulates both extrinsic (caspase-8/Bid) and intrinsic (caspase-9/cytochrome c release) mitochondrial apoptosis pathways.
  • Apoptosis induction by 3a protein is dependent on p38 MAPK activation, with the cytoplasmic domain being sufficient.
  • Increased Bax oligomerization and p53 levels were observed in 3a protein-expressing cells.
  • Inhibition of p38 MAPK attenuated 3a-induced apoptosis.
  • Nuclear translocation of STAT3 was blocked in cells expressing the 3a protein.

Conclusions:

  • The SARS-CoV 3a protein is a key mediator of apoptosis, primarily through the p38 MAPK-dependent mitochondrial pathway.
  • The 3a protein disrupts cellular processes, including STAT3 signaling, contributing to viral pathology.
  • Understanding these mechanisms provides insights into SARS-CoV pathogenesis and potential therapeutic targets.

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