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

Identifieur interne : 001384 ( Ncbi/Checkpoint ); précédent : 001383; suivant : 001385

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

Auteurs : Tetsuya Mizutani [Japon] ; Shuetsu Fukushi ; Daisuke Iizuka ; Osamu Inanami ; Mikinori Kuwabara ; Hideaki Takashima ; Hiroshi Yanagawa ; Masayuki Saijo ; Ichiro Kurane ; Shigeru Morikawa

Source :

RBID : pubmed:16487305

Descripteurs français

English descriptors

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.

DOI: 10.1111/j.1574-695X.2005.00028.x
PubMed: 16487305


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pubmed:16487305

Le document en format XML

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<term>Animals</term>
<term>Apoptosis</term>
<term>Cell Proliferation</term>
<term>Chlorocebus aethiops</term>
<term>Gene Expression Regulation</term>
<term>Glycogen Synthase Kinase 3 (genetics)</term>
<term>Glycogen Synthase Kinase 3 (metabolism)</term>
<term>Humans</term>
<term>Phosphatidylinositol 3-Kinases (genetics)</term>
<term>Phosphatidylinositol 3-Kinases (metabolism)</term>
<term>Phosphorylation</term>
<term>Proto-Oncogene Proteins c-akt (genetics)</term>
<term>Proto-Oncogene Proteins c-akt (metabolism)</term>
<term>SARS Virus (pathogenicity)</term>
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<term>Apoptose</term>
<term>Cellules Vero</term>
<term>Glycogen Synthase Kinase 3 (génétique)</term>
<term>Glycogen Synthase Kinase 3 (métabolisme)</term>
<term>Humains</term>
<term>Phosphatidylinositol 3-kinases (génétique)</term>
<term>Phosphatidylinositol 3-kinases (métabolisme)</term>
<term>Phosphorylation</term>
<term>Prolifération cellulaire</term>
<term>Protéines proto-oncogènes c-akt (génétique)</term>
<term>Protéines proto-oncogènes c-akt (métabolisme)</term>
<term>Régulation de l'expression des gènes</term>
<term>Transduction du signal</term>
<term>Virus du SRAS (pathogénicité)</term>
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<term>Proto-Oncogene Proteins c-akt</term>
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<term>Protéines proto-oncogènes c-akt</term>
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<term>SARS Virus</term>
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<term>Apoptosis</term>
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<term>Chlorocebus aethiops</term>
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<term>Phosphorylation</term>
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<term>Apoptose</term>
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<term>Phosphorylation</term>
<term>Prolifération cellulaire</term>
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<div type="abstract" xml:lang="en">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.</div>
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<name sortKey="Takashima, Hideaki" sort="Takashima, Hideaki" uniqKey="Takashima H" first="Hideaki" last="Takashima">Hideaki Takashima</name>
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<name sortKey="Mizutani, Tetsuya" sort="Mizutani, Tetsuya" uniqKey="Mizutani T" first="Tetsuya" last="Mizutani">Tetsuya Mizutani</name>
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