Inhibition of cell proliferation by SARS-CoV infection in Vero E6 cells.

Abstract

Severe acute respiratory syndrome (SARS) is caused by SARS-coronavirus (SARS-CoV). Infection of Vero E6 cells with SARS-CoV inhibits cell proliferation. Our previous study indicated that Akt, which is poorly phosphorylated in confluent cultures of Vero E6 cells, is phosphorylated and then dephosphorylated upon infection by SARS-CoV. In the present study, we showed that a serine residue of Akt was phosphorylated in Vero E6 cells in subconfluent culture and that Akt was dephosphorylated rapidly after SARS-CoV infection without up-regulation of its phosphorylation. Phosphorylation of glycogen synthase kinase-3beta, which is one of the downstream targets of Akt, was prevented in SARS-CoV-infected cells. However, treatment with glycogen synthase kinase-3beta small interfering RNA indicated that the glycogen synthase kinase-3beta signaling pathway was not related to inhibition of cell proliferation. Treatment of Vero E6 cells with the phosphatidylinositol 3'-kinase/Akt inhibitor, LY294002, which induces dephosphorylation of Akt, inhibited cell proliferation. As shown in our previous studies, apoptosis occurred in virus-infected cells within 18 h postinfection. Cellular mRNA transcription, which was reported to be up-regulated in SARS-CoV-infected Caco-2 cells, was not up-regulated in virus-infected Vero E6 cells, partially as a result of apoptosis. These results suggested that inhibition of cell proliferation is regulated by both the phosphatidylinositol 3'-kinase/Akt signaling pathway and by apoptosis in SARS-CoV-infected Vero E6 cells. This is the first study to analyze SARS-CoV-induced cell growth inhibition.

• Authors: Tetsuya Mizutani, Shuetsu Fukushi, Daisuke Iizuka, Osamu Inanami, Mikinori Kuwabara, Hideaki Takashima, Hiroshi Yanagawa, Masayuki Saijo, Ichiro Kurane, Shigeru Morikawa
• Journal: FEMS immunology and medical microbiology (FEMS Immunol Med Microbiol) Vol. 46 Issue 2 Pg. 236-43 (Mar 2006) ISSN: 0928-8244 [Print] England
• PMID: 16487305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3

Topics

• Animals
• Apoptosis
• Cell Proliferation
• Chlorocebus aethiops
• Gene Expression Regulation
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Humans
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Severe acute respiratory syndrome-related coronavirus (pathogenicity)
• Signal Transduction
• Vero Cells