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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79 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)405-415
頁數11
期刊Journal of Infectious Diseases
196
發行號3
DOIs
出版狀態已發佈 - 8月 1 2007
對外發佈

ASJC Scopus subject areas

  • 免疫學和過敏
  • 傳染性疾病

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