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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2007 Aug 10

PMID 17686858

Citations 59

Authors

Scott R Schaecher

Erin Touchette

Jill Schriewer

R Mark Buller

Andrew Pekosz

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread.

Becker M, Martin-Sancho L, Simons L, McRaven M, Chanda S, Hultquist J Nat Commun. 2024; 15(1):9480.

PMID: 39488529 PMC: 11531594. DOI: 10.1038/s41467-024-53791-4.

SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.

Deshpande R, Li W, Li T, Fanning K, Clemens Z, Nyunoya T Int J Mol Sci. 2024; 25(2).

PMID: 38256231 PMC: 10816122. DOI: 10.3390/ijms25021157.

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants.

de Melo G, Perraud V, Alvarez F, Vieites-Prado A, Kim S, Kergoat L Nat Commun. 2023; 14(1):4485.

PMID: 37495586 PMC: 10372078. DOI: 10.1038/s41467-023-40228-7.

Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.

Hurtado-Tamayo J, Requena-Platek R, Enjuanes L, Bello-Perez M, Sola I Front Cell Infect Microbiol. 2023; 13:1166839.

PMID: 37197199 PMC: 10183600. DOI: 10.3389/fcimb.2023.1166839.

Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.

Werbel W, Karaba A, Chiang T, Massie A, Brown D, Watson N Am J Transplant. 2023; 23(6):744-758.

PMID: 36966905 PMC: 10037915. DOI: 10.1016/j.ajt.2023.03.014.

References

Chan W, Wu C, Chow S, Cheung T, To K, Leung W . Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS). Mod Pathol. 2005; 18(11):1432-9. PMC: 7100671. DOI: 10.1038/modpathol.3800439. View

Li W, Shi Z, Yu M, Ren W, Smith C, Epstein J . Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005; 310(5748):676-9. DOI: 10.1126/science.1118391. View

Yang Y, Xiong Z, Zhang S, Yan Y, Nguyen J, Ng B . Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J. 2005; 392(Pt 1):135-43. PMC: 1317672. DOI: 10.1042/BJ20050698. View

Yount B, Roberts R, Sims A, Deming D, Frieman M, Sparks J . Severe acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice. J Virol. 2005; 79(23):14909-22. PMC: 1287583. DOI: 10.1128/JVI.79.23.14909-14922.2005. View

Sims A, Baric R, Yount B, Burkett S, Collins P, Pickles R . Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol. 2005; 79(24):15511-24. PMC: 1316022. DOI: 10.1128/JVI.79.24.15511-15524.2005. View

Chow K, Yeung Y, Hon C, Zeng F, Law K, Leung F . Adenovirus-mediated expression of the C-terminal domain of SARS-CoV spike protein is sufficient to induce apoptosis in Vero E6 cells. FEBS Lett. 2005; 579(30):6699-704. PMC: 7094440. DOI: 10.1016/j.febslet.2005.10.065. View

Huang C, Narayanan K, Ito N, Peters C, Makino S . Severe acute respiratory syndrome coronavirus 3a protein is released in membranous structures from 3a protein-expressing cells and infected cells. J Virol. 2005; 80(1):210-7. PMC: 1317539. DOI: 10.1128/JVI.80.1.210-217.2006. View

Kopecky-Bromberg S, Martinez-Sobrido L, Palese P . 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. J Virol. 2005; 80(2):785-93. PMC: 1346853. DOI: 10.1128/JVI.80.2.785-793.2006. View

Yuan X, Wu J, Shan Y, Yao Z, Dong B, Chen B . SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway. Virology. 2005; 346(1):74-85. PMC: 7111786. DOI: 10.1016/j.virol.2005.10.015. View

10.

Lin C, Lin K, Hsieh T, Shiu S, Li J . Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol. 2006; 46(3):375-80. PMC: 7110344. DOI: 10.1111/j.1574-695X.2006.00045.x. View

11.

Yin H, Wang H, Zong H, Chen X, Wang Y, Yun X . SGT, a Hsp90beta binding partner, is accumulated in the nucleus during cell apoptosis. Biochem Biophys Res Commun. 2006; 343(4):1153-8. DOI: 10.1016/j.bbrc.2006.03.090. View

12.

Fielding B, Gunalan V, Tan T, Chou C, Shen S, Khan S . Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT. Biochem Biophys Res Commun. 2006; 343(4):1201-8. PMC: 7092935. DOI: 10.1016/j.bbrc.2006.03.091. View

13.

Lai C, Chan Z, Yang D, Lo W, Lai Y, Chang M . Accelerated induction of apoptosis in insect cells by baculovirus-expressed SARS-CoV membrane protein. FEBS Lett. 2006; 580(16):3829-34. PMC: 7094299. DOI: 10.1016/j.febslet.2006.06.003. View

14.

Subbarao K, Roberts A . Is there an ideal animal model for SARS?. Trends Microbiol. 2006; 14(7):299-303. PMC: 7119110. DOI: 10.1016/j.tim.2006.05.007. View

15.

Huang C, Ito N, Tseng C, Makino S . Severe acute respiratory syndrome coronavirus 7a accessory protein is a viral structural protein. J Virol. 2006; 80(15):7287-94. PMC: 1563709. DOI: 10.1128/JVI.00414-06. View

16.

Zhao G, Shi S, Yang Y, Peng J . M and N proteins of SARS coronavirus induce apoptosis in HPF cells. Cell Biol Toxicol. 2006; 22(5):313-22. PMC: 7087820. DOI: 10.1007/s10565-006-0077-1. View

17.

Xu W, Roos A, Daha M, van Kooten C . Dendritic cell and macrophage subsets in the handling of dying cells. Immunobiology. 2006; 211(6-8):567-75. DOI: 10.1016/j.imbio.2006.05.023. View

18.

Yuste V, Bayascas J, Llecha N, Sanchez-Lopez I, Boix J, Comella J . The absence of oligonucleosomal DNA fragmentation during apoptosis of IMR-5 neuroblastoma cells: disappearance of the caspase-activated DNase. J Biol Chem. 2001; 276(25):22323-31. DOI: 10.1074/jbc.M100072200. View

19.

Ferri K, Kroemer G . Organelle-specific initiation of cell death pathways. Nat Cell Biol. 2001; 3(11):E255-63. DOI: 10.1038/ncb1101-e255. View

20.

Chen W, Calvo P, Malide D, Gibbs J, Schubert U, Bacik I . A novel influenza A virus mitochondrial protein that induces cell death. Nat Med. 2001; 7(12):1306-12. DOI: 10.1038/nm1201-1306. View