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Mechanisms of establishment of persistent SARS-CoV-infected cells

Tetsuya Mizutani1, Shuetsu Fukushi, Koji Ishii

  • 1Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan. tmizutan@nih.go.jp

Biochemical and Biophysical Research Communications
|July 1, 2006
PubMed

Insights

Persistent SARS-CoV infection involves apoptosis escape. The JNK and PI3K/Akt pathways, along with Bcl-2 proteins, are crucial for maintaining infected cells and establishing persistence, particularly through the SARS-CoV nucleocapsid protein.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Persistent SARS-CoV infection can arise after cellular apoptosis.
  • Early SARS-CoV infection stages rely on JNK and PI3K/Akt pathways for persistence.
  • Mechanisms underlying persistent SARS-CoV infection establishment remain incompletely understood.

Purpose of the Study:

  • To investigate signaling pathways involved in apoptosis escape in SARS-CoV-infected cells.
  • To identify key molecular players in the establishment and maintenance of persistent SARS-CoV infection.

Main Methods:

  • Analysis of signaling pathways (PI3K/Akt, JNK, p38 MAPK) and apoptosis-related proteins (Bcl-2, Bcl-xL) in persistently infected cells.
  • Treatment of infected cells with JNK-specific inhibitor (SP600125) to assess pathway necessity.
  • Expression of SARS-CoV nucleocapsid (N) protein in Vero E6 cells to study pathway activation.

Main Results:

  • Persistently infected cells (50h.p.i.) showed phosphorylation of PI3K/Akt, JNK, p38 MAPK, and Bcl-2, with increased Bcl-2 and Bcl-xL protein levels.
  • JNK pathway inhibition at 50h.p.i. led to complete cell death, indicating its essential role in maintaining persistent infection.
  • SARS-CoV N protein expression induced Akt and JNK phosphorylation, suggesting their necessity for persistence establishment.

Conclusions:

  • The JNK signaling pathway is critical for the maintenance of persistently SARS-CoV-infected cells.
  • Akt, JNK, Bcl-2, and Bcl-xL are essential proteins for the survival of cells with persistent SARS-CoV infection.
  • SARS-CoV N protein plays a key role in establishing persistence by inducing Akt and JNK phosphorylation.

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