Over-expression of Severe Acute Respiratory Syndrome Coronavirus 3b Protein Induces Both Apoptosis and Necrosis in Vero E6 Cells

Overview

Journal Virus Res

Specialty Microbiology

Date 2006 Sep 13

PMID 16965829

Citations 42

Authors

Sehaam Khan

Burtram C Fielding

Timothy H P Tan

Chih-Fong Chou

Shuo Shen

Seng Gee Lim

Wanjin Hong

Yee-Joo Tan

Affiliations

Soon will be listed here.

Abstract

The genome of the severe acute respiratory syndrome coronavirus encodes for eight accessory viral proteins with no known homologues in other coronaviruses. One of these is the 3b protein, which is encoded by the second open reading frame in subgenomic RNA 3 and contains 154 amino acids. Here, a detailed time-course study was performed to compare the apoptosis and necrosis profiles induced by full-length 3b, a 3b mutant that was deleted by 30 amino acids from the C terminus (3bDelta124-154) and the classical apoptosis inducer, Bax. Our results showed that Vero E6 cells transfected with a construct for expressing 3b underwent necrosis as early as 6h after transfection and underwent simultaneous necrosis and apoptosis at later time-points. At all the time-points analysed, the apoptosis induced by the expression of 3b was less than the level induced by Bax but the level of necrosis was comparable. The 3bDelta124-154 mutant behaves in a similar manner indicating that the localization of the 3b protein does not seems to be important for the cell-death pathways since full-length 3b is localized predominantly to the nucleolus, while the mutant is found to be concentrated in the peri-nuclear regions. To our knowledge, this is the first report of the induction of necrosis by a SARS-CoV protein.

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References

Espinoza J, Cortes-Gutierrez M, Kuznar J . Necrosis of infectious pancreatic necrosis virus (IPNV) infected cells rarely is preceded by apoptosis. Virus Res. 2005; 109(2):133-8. DOI: 10.1016/j.virusres.2004.10.014. View

Greenough T, Carville A, Coderre J, Somasundaran M, Sullivan J, Luzuriaga K . Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus. Am J Pathol. 2005; 167(2):455-63. PMC: 1603565. DOI: 10.1016/S0002-9440(10)62989-6. View

Assuncao Guimaraes C, Linden R . Programmed cell deaths. Apoptosis and alternative deathstyles. Eur J Biochem. 2004; 271(9):1638-50. DOI: 10.1111/j.1432-1033.2004.04084.x. View

Tan Y, Lim S, Hong W . Characterization of viral proteins encoded by the SARS-coronavirus genome. Antiviral Res. 2005; 65(2):69-78. PMC: 7114173. DOI: 10.1016/j.antiviral.2004.10.001. View

Los M, Mozoluk M, Ferrari D, Stepczynska A, Stroh C, Renz A . Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell. 2002; 13(3):978-88. PMC: 99613. DOI: 10.1091/mbc.01-05-0272. View

Benedict C, Norris P, Ware C . To kill or be killed: viral evasion of apoptosis. Nat Immunol. 2002; 3(11):1013-8. DOI: 10.1038/ni1102-1013. View

Roberts A, Paddock C, Vogel L, Butler E, Zaki S, Subbarao K . Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans. J Virol. 2005; 79(9):5833-8. PMC: 1082763. DOI: 10.1128/JVI.79.9.5833-5838.2005. View

Hussain S, Pan J, Chen Y, Yang Y, Xu J, Peng Y . Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J Virol. 2005; 79(9):5288-95. PMC: 1082772. DOI: 10.1128/JVI.79.9.5288-5295.2005. View

Thomson B . Viruses and apoptosis. Int J Exp Pathol. 2001; 82(2):65-76. PMC: 2517702. DOI: 10.1111/j.1365-2613.2001.iep0082-0065-x. View

10.

Syntichaki P, Tavernarakis N . The biochemistry of neuronal necrosis: rogue biology?. Nat Rev Neurosci. 2003; 4(8):672-84. DOI: 10.1038/nrn1174. View

11.

Roberts A, Vogel L, Guarner J, Hayes N, Murphy B, Zaki S . Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters. J Virol. 2004; 79(1):503-11. PMC: 538722. DOI: 10.1128/JVI.79.1.503-511.2005. View

12.

Peiris J, Guan Y, Yuen K . Severe acute respiratory syndrome. Nat Med. 2004; 10(12 Suppl):S88-97. PMC: 7096017. DOI: 10.1038/nm1143. View

13.

Marra M, Jones S, Astell C, Holt R, Brooks-Wilson A, Butterfield Y . The Genome sequence of the SARS-associated coronavirus. Science. 2003; 300(5624):1399-404. DOI: 10.1126/science.1085953. View

14.

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

15.

Guo J, Petric M, Campbell W, McGeer P . SARS corona virus peptides recognized by antibodies in the sera of convalescent cases. Virology. 2004; 324(2):251-6. PMC: 7125913. DOI: 10.1016/j.virol.2004.04.017. View

16.

Kuiken T, Fouchier R, Schutten M, Rimmelzwaan G, van Amerongen G, van Riel D . Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003; 362(9380):263-70. PMC: 7112434. DOI: 10.1016/S0140-6736(03)13967-0. View

17.

Snijder E, Bredenbeek P, Dobbe J, Thiel V, Ziebuhr J, Poon L . Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol. 2003; 331(5):991-1004. PMC: 7159028. DOI: 10.1016/s0022-2836(03)00865-9. View

18.

Mori I, Nishiyama Y, Yokochi T, Kimura Y . Virus-induced neuronal apoptosis as pathological and protective responses of the host. Rev Med Virol. 2004; 14(4):209-16. DOI: 10.1002/rmv.426. View

19.

Miller L, Fox J . Apoptosis and porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol. 2004; 102(3):131-42. DOI: 10.1016/j.vetimm.2004.09.004. View

20.

Berger A, Drosten C, Doerr H, Sturmer M, Preiser W . Severe acute respiratory syndrome (SARS)--paradigm of an emerging viral infection. J Clin Virol. 2003; 29(1):13-22. PMC: 7128705. DOI: 10.1016/j.jcv.2003.09.011. View