Upregulation of Mitochondrial Gene Expression in PBMC from Convalescent SARS Patients
The observations that Lymphopenia is common in severe acute respiratory syndrome (SARS) patients and that peripheral blood mononuclear cell (PBMC) could be infected by SARS-CoV indicate that PBMC could be useful in identifying the gene expression profile in convalescent patients and tracing the host response to SARS-CoV infection. In this study, the altered genes expressions in the PBMC of convalescent SARS patients were investigated with suppression subtractive hybridization (SSH). We found that genes encoded by mitochondrial DNA (mtDNA) were obviously upregulated, while mitochondria were now found to be closely connected with antiviral immunity. The identification of a viral gene, M, in SSH cDNA library shows the long-term existence of SARS-CoV in vivo. In addition, some oxidative stress sensitive genes, heat shock proteins, transcription factors, and cytokines showed remarkable elevation. Thin-section electron microscope shows increased lysosome-like granule and mitochondria in PBMC of patients. These results provide important intracellular clue for tracing host response to SARS-CoV infection and suggest a role of mitochondria in that process.
KEY WORDSSevere acute respiratory syndrome peripheral blood mononuclear cell suppression subtractive hybridization mitochondria
We thank the SARS affected staffs of the second affiliated hospital of Sun Yat-Sen University for their cooperation with this study. This work was partially supported by the ‘973’ National Key Program for Developing Basic Research (No. 2003CB514110), by the anti-SARS grant from Guangdong Province, and by the European Commission's Sixth Framework Programme under contract number 511060—Development of Intervention Strategies against SARS in a European-Chinese Taskforce (DISSECT).
- 1.Peiris JSM, Lai ST, Poon LLM, Guan Y, Yam LYC, Lim W, Nicholls J, Yee WKS, Yan WW, Cheung MT, Cheng VCC, Chan KH, Tsang DNC, Yung RWH, Ng TK, Yuen KY, and members of the SARS study group: Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361:1319–1325, 2003Google Scholar
- 2.Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Corner JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ, SARS Working Group: A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348:1953–1966, 2003Google Scholar
- 19.Donnelly CA, Ghani AC, Leung GM, Hedley AJ, Fraser C, Riley S, Abu-Raddad LJ, Ho LM, Thach TQ, Chau P, Chan KP, Lam TH, Tse LY, Tsang T, Liu SH, Kong JH, Lau EM, Ferguson NM, Anderson RM: Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet 361(9371):1761–1766, 2003. [Erratum in: Lancet 361(9371):1832, 2003]Google Scholar
- 21.Miro O, Lopez S, Rodriguez de la Concepcion M, Martinez E, Pedrol E, Garrabou G, Giralt M, Cardellach F, Gatell JM, Vilarroya F, Casademont J: Upregulatory mechanisms compensate for mitochondrial DNA depletion in asymptomatic individuals receiving stavudine plus didanosine. J Acquir Immune Defic Syndr 37(5):1550–1555, 2004PubMedGoogle Scholar
- 23.Miro O, Lopez S, Martinez E, Pedrol E, Milinkovic A, Deig E, Garrabou G, Casademont J, Gatell JM, Cardellach F: Mitochondrial effects of HIV infection on the peripheral blood mononuclear cells of HIV-infected patients who were never treated with antiretrovirals. Clin Infect Dis 39(5):710–716, 2004PubMedCrossRefGoogle Scholar
- 39.Quinlan G, Upton R: Oxidant–antioxidant balance in acute respiratory distress syndrome. In: European Respiratory Monograph: ARDS, T Evans, M Griffiths, B. Keogh (eds). European Respiratory Journals Ltd., 2002, pp 33–46Google Scholar
- 41.Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K, Jayawardena S, De Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G: Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119(4):529–542, 2004PubMedCrossRefGoogle Scholar
- 44.Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM: A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11:875–879, 2005PubMedCrossRefGoogle Scholar
- 47.Forrest MS, Lan Q, Hubbard AE, Zhang L, Vermeulen R, Zhao X, Li G, Wu YY, Shen M, Yin S, Chanock SJ, Rothman N, Smith MT: Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers. Environ Health Perspect 113(6):801–807, 2005PubMedCrossRefGoogle Scholar