Top

Published in:

01-11-2006

Upregulation of Mitochondrial Gene Expression in PBMC from Convalescent SARS Patients

Authors: HONGWEI SHAO, DONGMING LAN, ZHAOHUI DUAN, ZEHUAN LIU, JUN MIN, LICHUN ZHANG, JIAN HUANG, JING SU, SHANGWU CHEN, ANLONG XU

Published in: Journal of Clinical Immunology | Issue 6/2006

Abstract

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.

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, 2003

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, 2003

El-Sahly HM, Atmar RL, Glezen WP, Greenberg SB: Spectrum of clinical illness in hospitalized patients with “Common Cold” virus infections. Clin Infect Dis 31:96–100, 2000PubMedCrossRef

Falsey AR, Walsh EE, Hayden FG: Rhinovirus and coronavirus infection associated hospitalizations among older adults. J Infect Dis 185:1338–1341, 2002PubMedCrossRef

Bastien N, Robinson JL, Tse A, Lee BE, Hart L, Li Y: Human coronavirus NL-63 infections in children: A 1-year study. J Clin Microbiol 43:4567–4573, 2005PubMedCrossRef

Li WH, Moore MJ, Vasilieva N, Sui JH, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454, 2003PubMedCrossRef

Hofmann H, Pyrc K, Van Der Hoek L, Geier M, Berkhout B, Pohlmann S: Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci USA 102:7988–7993, 2005PubMedCrossRef

Chiu WK, Cheung PC, Ng KL, Ip PL, Sugunan VK, Luk DC, Ma LC, Chan BH, Lo KL, Lai WM: Severe acute respiratory syndrome in children: Experience in a regional hospital in Hong Kong. Pediatr Crit Care Med 4:279–283, 2003PubMedCrossRef

Lo AW, Tang NL, To KF: How the SARS coronavirus causes disease: Host or organism? J Pathol 208(2):142–151, 2006PubMedCrossRef

10.

Li L, Wo J, Shao J, Zhu H, Wu N, Li M, Yao H, Hu M, Dennin RH: SARS-coronavirus replicates in mononuclear cells of peripheral blood (PBMC) from SARS patients. J Clin Virol 28:239–244, 2003PubMedCrossRef

11.

Li TS, Qiu ZF, Zhang LQ, Han Y, He W, Liu ZY, Ma XJ, Fan HW, Lu W, Xie J, Wang H, Deng G, Wang A: Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis 189:648–651, 2004PubMedCrossRef

12.

McWhirter SM, Tenoever BR, Maniatis T: Connecting mitochondria and innate immunity. Cell 122(5):645–647, 2005PubMedCrossRef

13.

Seth RB, Sun L, Chen ZJ: Antiviral innate immunity pathways. Cell Res 16(2):141–147, 2006PubMedCrossRef

14.

Liu W, Tang F, Fontanet A, Zhan L, Zhao QM, Zhang PH, Wu XM, Zuo SQ, Baril L, Vabret A, Xin ZT, Shao YM, Yang H, Cao WC: Long-term SARS coronavirus excretion from patient cohort, China. Emerg Infect Dis 10(10):1841–1843, 2004PubMed

15.

Chu CM, Leung WS, Cheng VC, Chan KH, Lin AW, Chan VL, Lam JY, Chan KS, Yuen KY: Duration of RT-PCR positivity in severe acute respiratory syndrome. Eur Respir J 25(1):12–14, 2005PubMedCrossRef

16.

Clayton DA: Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol 7:453–478, 1991PubMedCrossRef

17.

Ojala D, Crews S, Montoya J, Gelfand R, Attardi G: A small polyadenylated RNA (7 S RNA), containing a putative ribosome attachment site, maps near the origin of human mitochondrial DNA replication. J Mol Biol 150(2):303–314, 1981PubMedCrossRef

18.

Lee DY, Clayton DA: RNase mitochondrial RNA processing correctly cleaves a novel R loop at the mitochondrial DNA leading-strand origin of replication. Genes Dev 11(5):582–592, 1997PubMed

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]

20.

Kakuda TN: Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther 22:685–708, 2000PubMedCrossRef

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, 2004PubMed

22.

Van Itallie CM: Thyroid hormone and dexamethasone increase the levels of a messenger ribonucleic acid for a mitochondrially encoded subunit but not for a nuclear-encoded subunit of cytochrome c oxidase. Endocrinology 127(1):55–62, 1990PubMedCrossRef

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, 2004PubMedCrossRef

24.

Yuan X, Shan Y, Yao Z, Li J, Zhao Z, Chen J, Cong Y: Mitochondrial location of severe acute respiratory syndrome coronavirus 3b protein. Mol Cells 21(2):186–191, 2006PubMed

25.

Li Q, Wang L, Dong C, Che Y, Jiang L, Liu L, Zhao H, Liao Y, Sheng Y, Dong S, Ma S: The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect. J Clin Virol 34(2):133–139, 2005PubMedCrossRef

26.

Seth RB, Sun L, Ea CK, Chen ZJ: Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF3. Cell 122(5):669–682, 2005PubMedCrossRef

27.

Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB: VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19(6):727–740, 2005PubMedCrossRef

28.

Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S: IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6(10):981–988, 2005PubMedCrossRef

29.

Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J: Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437(7062):1167–1172, 2005PubMedCrossRef

30.

Yedavalli VS, Shih HM, Chiang YP, Lu CY, Chang LY, Chen MY, Chuang CY, Dayton AI, Jeang KT, Huang LM: Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1. J Virol 79(21):13735–13746, 2005PubMedCrossRef

31.

Carr SM, Carnero E, Garcia-Sastre A, Brownlee GG, Fodor E: Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses. Virology 344(2):492–508, 2006PubMedCrossRef

32.

Su J, Wang G, Barrett JW, Irvine TS, Gao X, McFadden G: Myxoma virus M11L blocks apoptosis through inhibition of conformational activation of Bax at the mitochondria. J Virol 80(3):1140–1151, 2006PubMedCrossRef

33.

Hiraragi H, Kim SJ, Phipps AJ, Silic-Benussi M, Ciminale V, Ratner L, Green PL, Lairmore MD: Human T-lymphotropic virus type 1 mitochondrion-localizing protein p13(II) is required for viral infectivity in vivo. J Virol 80(7):3469–3476, 2006PubMedCrossRef

34.

Miranda S, Foncea R, Guerrero J, Leighton F: Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells. Biochem Biophys Res Commun 258(1):44–49, 1999PubMedCrossRef

35.

Lee HC, Yin PH, Lu CY, Chi CW, Wei YH: Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J 348(Pt 2):425–432, 2000PubMedCrossRef

36.

Suliman HB, Carraway MS, Welty-Wolf KE, Whorton AR, Piantados CA: Lipopolysaccharide stimulates mitochondrial biogenesis via activation of nuclear respiratory factor-1. J Biol Chem 278:41510–41518, 2003PubMedCrossRef

37.

Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST, Leung CY, Chu CM, Hui PK, Mak KL, Lim W, Yan KW, Chan KH, Tsang NC, Guan Y, Yuen KY, Peiris JS: Lung pathology of fatal severe acute respiratory syndrome. Lancet 361:1773–1778, 2003PubMedCrossRef

38.

Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J, Li X, Kang W, Weng D, Lu Y, Wu D, He L, Yao K: The clinical pathology of severe acute respiratory syndrome (SARS): A report from China. J Pathol 200:282–289, 2003PubMedCrossRef

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 33–46

40.

Rabilloud T, Heller M, Gasnier F, Luche S, Rey C, Aebersold R, Benahmed M, Louisot P, Lunardi J: Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site. J Biol Chem 277(22):19396–19401, 2002PubMedCrossRef

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, 2004PubMedCrossRef

42.

Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP, Melendez AJ: Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. BMC Immunol 6:2, 2005PubMedCrossRef

43.

Rao GN, Berk BC: Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. Circ Res 70(3):593–599, 1992PubMed

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, 2005PubMedCrossRef

45.

Wu S, Gao J, Ohlemeyer C, Roos D, Niessen H, Kottgen E, Gessner R: Activation of AP-1 through reactive oxygen species by angiotensin II in rat cardiomyocytes. Free Radic Biol Med 39(12):1601–1610, 2005PubMedCrossRef

46.

He R, Leeson A, Andonov A, Li Y, Bastien N, Cao J, Osiowy C, Dobie F, Cutts T, Ballantine M, Li X: Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein. Biochem Biophys Res Commun 311:870–876, 2003PubMedCrossRef

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, 2005PubMedCrossRef

48.

Sheets P, Carlson G: Kinetic factors involved in the metabolism of benzene in mouse lung and liver. J Toxicol Environ Health A 67(5):421–430, 2004PubMed

49.

Rana SV, Verma Y: Biochemical toxicity of benzene. J Environ Biol 26(2):157–168, 2005PubMed

Title: Upregulation of Mitochondrial Gene Expression in PBMC from Convalescent SARS Patients
Authors: HONGWEI SHAO
DONGMING LAN
ZHAOHUI DUAN
ZEHUAN LIU
JUN MIN
LICHUN ZHANG
JIAN HUANG
JING SU
SHANGWU CHEN
ANLONG XU
Publication date: 01-11-2006
Publisher: Kluwer Academic Publishers-Plenum Publishers
Published in: Journal of Clinical Immunology / Issue 6/2006
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-006-9046-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2006

Double Reactivity Against Actin and α-Actinin Defines a Severe Form of Autoimmune Hepatitis Type 1

Type I Interferons Attenuate T Cell Activating Functions of Human Mast Cells by Decreasing TNF-α Production and OX40 Ligand Expression While Increasing IL-10 Production

Detection of Cellular Immunity to Rabies Antigens in Human Vaccinees

Programmed Death-1 Gene Polymorphisms in Patients With Systemic Lupus Erythematosus in Taiwan

Frequency and Clinical Manifestations of Patients with Primary Immunodeficiency Disorders in Iran: Update from the Iranian Primary Immunodeficiency Registry

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials