Open AccessInhibition of cell proliferation by SARS‐CoV infection in Vero E6 cells
Author(s) -
Mizutani Tetsuya,
Fukushi Shuetsu,
Iizuka Daisuke,
Inanami Osamu,
Kuwabara Mikinori,
Takashima Hideaki,
Yanagawa Hiroshi,
Saijo Masayuki,
Kurane Ichiro,
Morikawa Shigeru
Publication year - 2006
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2005.00028.x
Subject(s) - vero cell , virology , biology , covid-19 , microbiology and biotechnology , cell growth , cell culture , virus , medicine , infectious disease (medical specialty) , genetics , disease , pathology
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‐3β, which is one of the downstream targets of Akt, was prevented in SARS‐CoV‐infected cells. However, treatment with glycogen synthase kinase‐3β small interfering RNA indicated that the glycogen synthase kinase‐3β 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.