Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics

Bordi, Licia; Castilletti, Concetta; Falasca, Laura; Ciccosanti, Fabiola; Calcaterra, Silvia; Rozera, Gabriella; Di, Antonino; Zaniratti, S.; Rinaldi, Alessandra; Ippolito, Giuseppe; Piacentini, Mauro; Capobianchi, Maria Rosaria

doi:10.1007/s00705-005-0632-8

Cited by 41 publications

(51 citation statements)

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“…We showed that over-expression of 3a induced apoptosis in Drosophila, and the results were consistent with a parallel investigation in mammalian cells [17]. It is well known that SARS-CoV infection induces apoptosis in viral-infected cells [4,11,[13][14][15] and the pro-apoptotic properties of a number of individual viral proteins have recently been revealed [12,[16][17][18][19][20][21][22]. All these Wndings illustrate that non-mammalian systems, particularly Drosophila in this study, are plausible models for the studies of viral gene functions in vivo.…”

Section: Discussionsupporting

confidence: 88%

“…It is well known that SARS-CoV infection induces apoptosis in viral-infected cells [4,11,[13][14][15] and the pro-apoptotic properties of a number of individual viral proteins have recently been revealed [12,[16][17][18][19][20][21][22]. At the mechanistic level, SARS-CoV infection has been shown to interfere with the Bcl-2 anti-apoptotic pathway [15]. Swelling of mitochondria is also found in viral-infected cells [13] which indicates a mitochondrial involvement in SARS-CoV-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The SARS-CoV genome contains [13][14][15] open reading frames (ORFs) [1][2][3] which encode the ORF1a-1b (replicases and protease enzymes), Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N), and a number of less well-characterized regulatory proteins [1,2]. The SARS-CoV genome contains [13][14][15] open reading frames (ORFs) [1][2][3] which encode the ORF1a-1b (replicases and protease enzymes), Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N), and a number of less well-characterized regulatory proteins [1,2].…”

mentioning

confidence: 99%

“…The SARS-CoV genome contains [13][14][15] open reading frames (ORFs) [1][2][3] which encode the ORF1a-1b (replicases and protease enzymes), Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N), and a number of less well-characterized regulatory proteins [1,2]. Apoptosis is a main pathologic feature induced by SARS-CoV infection [4,11,[13][14][15], and a number of SARS-CoV proteins have been shown to be pro-apoptotic [12,[16][17][18][19][20][21][22]. Apoptosis is a main pathologic feature induced by SARS-CoV infection [4,11,[13][14][15], and a number of SARS-CoV proteins have been shown to be pro-apoptotic [12,[16][17][18][19][20][21][22].…”

mentioning

confidence: 99%

“…Previous studies revealed that SARS-CoV infection triggers a number of cellular responses in infected cells including modulation of signal transduction cascades such as the p38 MAPK and Akt cell survival pathways [4][5][6][7][8][9][10][11][12], and induction of apoptosis [11,13,14]. Apoptosis induction has further been demonstrated to initiate viral cytopathic eVect (CPE) 1 in the infected cells [13] but appears not to be a mechanism for dissemination of new virions [15]. Apoptosis induction has further been demonstrated to initiate viral cytopathic eVect (CPE) 1 in the infected cells [13] but appears not to be a mechanism for dissemination of new virions [15].…”

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confidence: 99%

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The SARS-Coronavirus Membrane protein induces apoptosis through modulating the Akt survival pathway

Chan

et al. 2007

Archives of Biochemistry and Biophysics

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A number of viral gene products are capable of triggering apoptotic cell death through interfering with cellular signaling cascades, including the Akt kinase pathway. In this study, the pro-apoptotic role of the SARS-CoV Membrane (M) structural protein is described. We found that the SARS-CoV M protein induced apoptosis in both HEK293T cells and transgenic Drosophila. We further showed that M protein-induced apoptosis involved mitochondrial release of cytochrome c protein, and could be suppressed by caspase inhibitors. Over-expression of M caused a dominant rough-eye phenotype in adult Drosophila. By performing a forward genetic modifier screen, we identified phosphoinositide-dependent kinase-1 (PDK-1) as a dominant suppressor of M-induced apoptotic cell death. Both PDK-1 and Akt kinases play essential roles in the cell survival signaling pathway. Altogether, our data show that SARS-CoV M protein induces apoptosis through the modulation of the cellular Akt pro-survival pathway and mitochondrial cytochrome c release.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…The SARS-CoV genome contains [13][14][15] open reading frames (ORFs) [1][2][3] which encode the ORF1a-1b (replicases and protease enzymes), Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N), and a number of less well-characterized regulatory proteins [1,2]. Apoptosis is a main pathologic feature induced by SARS-CoV infection [4,11,[13][14][15], and a number of SARS-CoV proteins have been shown to be pro-apoptotic [12,[16][17][18][19][20][21][22]. Apoptosis is a main pathologic feature induced by SARS-CoV infection [4,11,[13][14][15], and a number of SARS-CoV proteins have been shown to be pro-apoptotic [12,[16][17][18][19][20][21][22].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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The SARS-Coronavirus Membrane protein induces apoptosis through modulating the Akt survival pathway

Chan

et al. 2007

Archives of Biochemistry and Biophysics

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Molecular Biology of the SARS-Coronavirus

Lal

2010

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The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.Cover Illustration: 3D model of SARS-CoV, with a wedge cut out of it to reveal the nucleocapsid (see Chap. 3 by Daniel R. Beniac and Timothy F. Booth)Background: HL-CZ cells transfected with SARS-CoV Spike construct and incubated with anti-Spike human monoclonal antibody followed by secondary FITC-labeled anti-human antibody (see Chap. 18 by T. Narasaraju, P.L. Soong, J. ter Meulen, J. Goudsmit and Vincent T.K. Chow)Cover design: WMXDesign GmbH, Heidelberg, GermanyPrinted on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword SARS was the first new plague of the twenty-first century. Within months, it spread worldwide from its "birthplace" in Guangdong Province, China, affecting over 8,000 people in 25 countries and territories across five continents. SARS exposed the vulnerability of our modern globalised world to the spread of a new emerging infection. SARS (or a similar new emerging disease) could neither have spread so rapidly nor had such a great global impact even 50 years ago, and arguably, it was itself a product of our global inter-connectedness. Increasing affluence and a demand for wild-game as exotic food led to the development of large trade of live animal and game animal markets where many species of wild and domestic animals were co-housed, providing the ideal opportunities for inter-species transmission of viruses and other microbes. Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease. Health-care itself has become a two-edged sword.While SARS exposed the vulnerabilities of the modern human condition, it also highlighted the global capacity for a rapid public health and scientific response to an emerging infectious disease threat. Public health and scientific responses succeeded in identifying the causative agent, developing diagnostic tests, and interrupting the spread of the outbreak. The complete virus genome was fully deciphered within weeks and in the ensuing months and years saw an outpouring of scientific research about the disease and its causative agent, the SARS coronavirus. The natural animal reservoir (bats) and amplifier hosts were defined, the virus receptor on human cell...

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Molecular and Biochemical Characterization of the SARS-CoV Accessory Proteins ORF8a, ORF8b and ORF8ab

Keng¹,

Tan²

2009

Molecular Biology of the SARS-Coronavirus

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A novel coronavirus was identified as the aetiological agent for the global outbreak of severe acute respiratory syndrome (SARS) at the beginning of the twenty-first century. The SARS coronavirus genome encodes for proteins that are common to all members of the coronavirus, i.e. replicase polyproteins (pp1a and pp1b) and structural proteins (spike, membrane, nucleocapsid and envelope), as well as eight accessory proteins. The accessory proteins have been designated as open reading frames (ORF) 3a, 3b, 6, 7a, 7b, 8a, 8b and 9b, and they do not show significant homology to viral proteins of other known coronaviruses. Epidemiological studies have revealed that the part of the viral genome that encodes for ORF8a and ORF8b showed major variations and the animal isolates contain an additional 29-nucleotide sequence which is absent in most of the human isolates. As a result, ORF8a and ORF8b in the human isolates become one ORF, termed ORF8ab. In this chapter, we will discuss the genetic variation in the ORF8 region, expression of ORF8a, ORF8b and ORF8ab during infection, cellular localization and posttranslational modification of ORF8a, ORF8b and ORF8ab, participation of ORF8a, ORF8b and ORF8ab in viral-viral interactions, their effects on other viral proteins and impact on viral replication and/or pathogenesis.

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Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics

Cited by 41 publications

References 27 publications

The SARS-Coronavirus Membrane protein induces apoptosis through modulating the Akt survival pathway

The SARS-Coronavirus Membrane protein induces apoptosis through modulating the Akt survival pathway

Molecular Biology of the SARS-Coronavirus

Molecular and Biochemical Characterization of the SARS-CoV Accessory Proteins ORF8a, ORF8b and ORF8ab

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