Severe acute respiratory syndrome coronavirus gene 7 products contribute to virus-induced apoptosis.
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.
Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, 660 S. Euclid Ave., Campus Box 8230, St. Louis, Missouri 63110, USA.
Scott R
SR
Schaecher
Erin
E
Touchette
Jill
J
Schriewer
R Mark
RM
Buller
Andrew
A
Pekosz
D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D006224:Cricetinae; D006801:Humans; D020287:In Situ Nick-End Labeling; D008647:Mesocricetus; D016366:Open Reading Frames / Q000502:physiology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D017384:Sequence Deletion; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology* / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D014764:Viral Proteins