M and N proteins of SARS coronavirus induce apoptosis in HPF cells

Tsoi

The International Journal of Biochemistry & Cell Biology

et al. 2009

112

The severe acute respiratory syndrome-coronavirus (SARS-CoV) caused an outbreak of atypical pneumonia in 2003. The SARS-CoV viral genome encodes several proteins which have no homology to proteins in any other coronaviruses, and a number of these proteins have been implicated in viral cytopathies. One such protein is 3a, which is also known as X1, ORF3 and U274. 3a expression is detected in both SARS-CoV infected cultured cells and patients. Among the different functions identified, 3a is a capable of inducing apoptosis. We previously showed that caspase pathways are involved in 3a-induced apoptosis. In this study, we attempted to find out protein domains on 3a that are essential for its pro-apoptotic function. Protein sequence analysis reveals that 3a possesses three major protein signatures, the cysteine-rich, Yxx phi and diacidic domains. We showed that 3a proteins carrying respective mutations in these protein domains exhibit reduced pro-apoptotic activities, indicating the importance of these domains on 3a's pro-apoptotic function. It was previously reported that 3a possesses potassium ion channel activity. We further demonstrated that the blockade of 3a's potassium channel activity abolished caspase-dependent apoptosis. This report provides the first evidence that ion channel activity of 3a is required for its pro-apoptotic function. As ion channel activity has been reported to regulate apoptosis in different pathologic conditions, finding ways to modulate the ion channel activity may offer a new direction toward the inhibition of apoptosis triggered by SARS-CoV.

Section: Introductionsupporting

confidence: 66%

The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function

Tsoi

The International Journal of Biochemistry & Cell Biology

et al. 2009

112

“…Many SARS-CoV proteins induce apoptosis and/or necrosis when expressed from cDNA (10,29,30,33,36,38,63,73,76,80,84). The mechanisms for induction of cell death by the viral proteins are not clear, and it is unknown if these proapoptotic events play a significant role in induction of cell death during virus infection.…”

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis

Schaecher¹,

Touchette

Schriewer

et al. 2007

J Virol

The proteins encoded by gene 7 of the severe acute respiratory syndrome coronavirus (SARS-CoV) have been demonstrated to have proapoptotic activity when expressed from cDNA but appear to be dispensable for virus replication. Recombinant SARS-CoVs bearing deletions in gene 7 were used to assess the contribution of gene 7 to virus replication and apoptosis in several transformed cell lines, as well as to replication and pathogenesis in golden Syrian hamsters. Deletion of gene 7 had no effect on SARS-CoV replication in transformed cell lines, nor did it alter the induction of early apoptosis markers such as annexin V binding and activation of caspase 3. However, viruses with gene 7 disruptions were not as efficient as wild-type virus in inducing DNA fragmentation, as judged by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, indicating that the gene 7 products do contribute to virus-induced apoptosis. Disruption of gene 7 did not affect virus replication or morbidity in golden Syrian hamsters, suggesting that the gene 7 products are not required for acute infection in vivo. The data indicate that open reading frames 7a and 7b contribute to but are not solely responsible for the apoptosis seen in SARS-CoV-infected cells.

Comparative Immunology, Microbiology and Infectious Diseases

“…SARS-CoV can induce apoptosis in the cultured cells and in the infected patient [44,57,[64][65][66][67][68]. A series of experimental evidence have indicated that several viral components from SARS-CoV are involved in apoptosis, one of consequences of the interplay between SARS-CoVs and its host cells [57,[64][65][66][67][68][69][70][71]. First, three structural proteins (S, N and M) have been suggested to contribute to inducing of apoptosis in different cell lines [57,65,68,70].…”

Section: Sars-cov Induced Apoptosismentioning

confidence: 99%

“…A series of experimental evidence have indicated that several viral components from SARS-CoV are involved in apoptosis, one of consequences of the interplay between SARS-CoVs and its host cells [57,[64][65][66][67][68][69][70][71]. First, three structural proteins (S, N and M) have been suggested to contribute to inducing of apoptosis in different cell lines [57,65,68,70]. Second, of 16 nsps of SARS-CoV, only 3CL pro (nsp3) is pointed out to function as an inducer of apoptosis in Vero-E6 cells [64].…”

Section: Sars-cov Induced Apoptosismentioning

confidence: 99%

Towards our understanding of SARS-CoV, an emerging and devastating but quickly conquered virus

Feng

Gao

2007

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus (SARS-CoV), which has overwhelmed more than 30 countries claiming nearly 8400 cases with over 800 fatalities. Thanks to the unprecedented international collaboration, the whole-genomes of SARS-CoVs were successfully deciphered shortly after the identification of the causative pathogen for outbreak of SARS in southern China, in 2003. Hitherto, the SARS-CoV, as a viral paradigm of emerging infectious entities, has been extensively studied that has ranged from epidemiology, molecular virology/immunology to structural genomics. Also, several lines of breakthroughs have been record-brokenly obtained, that included the finding of ACE2, a functional receptor for the SARS-CoV, solution of the 3CL(pro) structure, a first crystal structure of SARS-related macromolecules, revealing of bats as natural reservoirs for SARS-like viruses and the possible involvement of civet cats in the SARS emergence. This review intends to outline the major progress in the journey of SARS-related exploration, by emphasizing those inaugurated studies with milestone-like significance contributed by Chinese research groups.