Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients Free

Abstract

Metabolomics analysis of biofluids is increasingly being recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted H nuclear magnetic resonance may allow the anticipation of the occurrence of cytomegalovirus (CMV) DNAemia in allogeneic stem cell transplant. For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine -oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model in cross-validation technical replicates was 73 %. Increased levels of alanine, lactate and total fatty acids, and a shift in the fatty acid profile towards unsaturated species, were observed in patients with detectable CMV DNA in plasma. The classification accuracy of this PLS-DA model in cross-validation technical replicates was 81 %. Plasma metabolomics profiling may prove useful for identifying patients at highest risk for CMV DNAemia thus allowing early inception of antiviral therapy.

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2015-11-01
2024-03-29
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References

  1. Bodi V., Sanchis J., Morales J.M., Marrachelli V.G., Nuñez J., Forteza M.J., Chaustre F., Gomez C., Mainar L., other authors. 2012; Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models. J Am Coll Cardiol 59:1629–1641 [View Article][PubMed]
    [Google Scholar]
  2. Boeckh M., Murphy W.J., Peggs K.S. 2015; Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol Blood Marrow Transplant 21:24–29 [View Article][PubMed]
    [Google Scholar]
  3. Borrás C., Monleón D., López-Grueso R., Gambini J., Orlando L., Pallardó F.V., Santos E., Viña J., Font de Mora J. 2011; RasGrf1 deficiency delays aging in mice. Aging (Albany, NY) 3:262–276[PubMed]
    [Google Scholar]
  4. Clari M.Á., Bravo D., Costa E., Muñoz-Cobo B., Solano C., Remigia M.J., Giménez E., Benmarzouk-Hidalgo O.J., Pérez-Romero P., Navarro D. 2013; Comparison of the new Abbott Real Time CMV assay and the Abbott CMV PCR Kit for the quantitation of plasma cytomegalovirus DNAemia. Diagn Microbiol Infect Dis 75:207–209 [View Article][PubMed]
    [Google Scholar]
  5. Cook C.H., Trgovcich J., Zimmerman P.D., Zhang Y., Sedmak D.D. 2006; Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1beta triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol 80:9151–9158 [View Article][PubMed]
    [Google Scholar]
  6. Dumas M.E., Maibaum E.C., Teague C., Ueshima H., Zhou B., Lindon J.C., Nicholson J.K., Stamler J., Elliott P., other authors. 2006; Assessment of analytical reproducibility of 1H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study. Anal Chem 78:2199–2208 [View Article][PubMed]
    [Google Scholar]
  7. Giménez E., Muñoz-Cobo B., Solano C., Amat P., Navarro D., Tang Y.-W. 2014; Early kinetics of plasma cytomegalovirus DNA load in allogeneic stem cell transplant recipients in the era of highly sensitive real-time PCR assays: does it have any clinical value?. J Clin Microbiol 52:654–656 [View Article][PubMed]
    [Google Scholar]
  8. Holmes E., Loo R.L., Stamler J., Bictash M., Yap I.K., Chan Q., Ebbels T., De Iorio M., Brown I.J., other authors. 2008; Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453:396–400 [View Article][PubMed]
    [Google Scholar]
  9. Kamlage B., Maldonado S.G., Bethan B., Peter E., Schmitz O., Liebenberg V., Schatz P. 2014; Quality markers addressing preanalytical variations of blood and plasma processing identified by broad and targeted metabolite profiling. Clin Chem 60:399–412 [View Article][PubMed]
    [Google Scholar]
  10. Locci E., Noto A., Lanari M., Lazzarotto T., Fanos V., Atzori L. 2013; Metabolomics: a new tool for the investigation of metabolic changes induced by cytomegalovirus. J Matern Fetal Neonatal Med 26:(Suppl. 2)17–19 [View Article][PubMed]
    [Google Scholar]
  11. Michaeli B., Martinez A., Revelly J.P., Cayeux M.C., Chioléro R.L., Tappy L., Berger M.M. 2012; Effects of endotoxin on lactate metabolism in humans. Crit Care 16:R139 [View Article][PubMed]
    [Google Scholar]
  12. Mickiewicz B., Duggan G.E., Winston B.W., Doig C., Kubes P., Vogel H.J., Alberta Sepsis Network. 2014; Metabolic profiling of serum samples by 1H nuclear magnetic resonance spectroscopy as a potential diagnostic approach for septic shock. Crit Care Med 42:1140–1149 [View Article][PubMed]
    [Google Scholar]
  13. Munger J., Bennett B.D., Parikh A., Feng X.J., McArdle J., Rabitz H.A., Shenk T., Rabinowitz J.D. 2008; Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol 26:1179–1186 [View Article][PubMed]
    [Google Scholar]
  14. Noto A., Dessi A., Puddu M., Mussap M., Fanos V. 2014; Metabolomics technology and their application to the study of the viral infection. J Matern Fetal Neonatal Med 27:(Suppl. 2)53–57 [View Article][PubMed]
    [Google Scholar]
  15. Pacchiarotta T., Deelder A.M., Mayboroda O.A. 2012; Metabolomic investigations of human infections. Bioanalysis 4:919–925 [View Article][PubMed]
    [Google Scholar]
  16. Solano C., Navarro D. 2010; Clinical virology of cytomegalovirus infection following hematopoietic transplantation. Future Virol 5:111–124 [View Article]
    [Google Scholar]
  17. Tabas I., Glass C.K. 2013; Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 339:166–172 [View Article][PubMed]
    [Google Scholar]
  18. Tang W.H., Wang Z., Fan Y., Levison B., Hazen J.E., Donahue L.M., Wu Y., Hazen S.L. 2014; Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 64:1908–1914 [View Article][PubMed]
    [Google Scholar]
  19. Tilton C., Clippinger A.J., Maguire T., Alwine J.C. 2011; Human cytomegalovirus induces multiple means to combat reactive oxygen species. J Virol 85:12585–12593 [View Article][PubMed]
    [Google Scholar]
  20. Tormo N., Solano C., Benet I., Nieto J., de la Cámara R., López J., Garcia-Noblejas A., Muñoz-Cobo B., Costa E., other authors. 2011; Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT. Bone Marrow Transplant 46:1437–1443 [View Article][PubMed]
    [Google Scholar]
  21. Trygg J., Holmes E., Lundstedt T. 2007; Chemometrics in metabonomics. J Proteome Res 6:469–479 [View Article][PubMed]
    [Google Scholar]
  22. Vastag L., Koyuncu E., Grady S.L., Shenk T.E., Rabinowitz J.D. 2011; Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog 7:e1002124 [View Article][PubMed]
    [Google Scholar]
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