Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis

Chia Yen Chen, Yueh Hsin Ping, Hsin Chen Lee, Kuan Hsuan Chen, Yuan Ming Lee, Yu Juin Chan, Te Cheng Lien, Tjin Shing Jap, Chi Hung Lin, Lung Sen Kao, Yi Ming Arthur Chen

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36 Citations (Scopus)

Abstract

Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.

Original languageEnglish
Pages (from-to)405-415
Number of pages11
JournalJournal of Infectious Diseases
Volume196
Issue number3
DOIs
Publication statusPublished - Aug 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Chen, C. Y., Ping, Y. H., Lee, H. C., Chen, K. H., Lee, Y. M., Chan, Y. J., Lien, T. C., Jap, T. S., Lin, C. H., Kao, L. S., & Chen, Y. M. A. (2007). Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis. Journal of Infectious Diseases, 196(3), 405-415. https://doi.org/10.1086/519166