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

Padhan, Kartika ; Minakshi, Rinki ; Bin Towheed, Mohammad Aatif ; Jameel, Shahid (2008) Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation Journal of General Virology, 89 . pp. 1960-1969. ISSN 0022-1317

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Official URL: http://vir.sgmjournals.org/cgi/content/abstract/89...

Related URL: http://dx.doi.org/10.1099/vir.0.83665-0

Abstract

The molecular mechanisms governing severe acute respiratory syndrome coronavirus-induced pathology are not fully understood. Virus infection and some individual viral proteins, including the 3a protein, induce apoptosis. However, the cellular targets leading to 3a protein-mediated apoptosis have not been fully characterized. This study showed that the 3a protein modulates the mitochondrial death pathway in two possible ways. Activation of caspase-8 through extrinsic signal(s) caused Bid activation. In the intrinsic pathway, there was activation of caspase-9 and cytochrome c release from the mitochondria. This was the result of increased Bax oligomerization and higher levels of p53 in 3a protein-expressing cells, which depended on the activation of p38 MAP kinase (MAPK) in these cells. For p38 activation and apoptosis induction, the 3a cytoplasmic domain was sufficient. In direct Annexin V staining assays, the 3a protein-expressing cells showed increased apoptosis that was attenuated with the p38 MAPK inhibitor SB203580. A block in nuclear translocation of the STAT3 transcription factor in cells expressing the 3a protein was also observed. These results have been used to present a model of 3a-mediated apoptosis.

Item Type:Article
Source:Copyright of this article belongs to Society for General Microbiology.
ID Code:13121
Deposited On:11 Nov 2010 06:49
Last Modified:16 May 2016 22:20

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