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Abstract

Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.

Funding
This study was supported by the:
  • Health and Medical Research Fund (Award HKM-15-M03)
    • Principle Award Recipient: KelvinKai-Wang To
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. The Microbiology Society waived the open access fees for this article.
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2021-05-06
2024-04-19
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References

  1. Jain S, Self WH, Wunderink RG, Team CES. CDC EPIC Study Team Community-Acquired pneumonia requiring hospitalization. N Engl J Med 2015; 373:415–427 [View Article][PubMed]
    [Google Scholar]
  2. Hung IF, Zhang AJ, To KKW, Chan JF, Zhu SH et al. Unexpectedly higher morbidity and mortality of hospitalized elderly patients associated with rhinovirus compared with influenza virus respiratory tract infection. Int J Mol Sci 2017; 18:259 [View Article][PubMed]
    [Google Scholar]
  3. To KKW, Chan K-H, Ho J, Pang PKP, Ho DTY et al. Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study. Clin Microbiol Infect 2019; 25:1539–1545 [View Article][PubMed]
    [Google Scholar]
  4. DeMuri GP, Eickhoff JC, Gern JC, Wald ER. Clinical and virological characteristics of acute sinusitis in children. Clin Infect Dis 2019; 69:1764–1770 [View Article][PubMed]
    [Google Scholar]
  5. To KKW, Lau SK, Chan K-H, Mok K-Y, Luk HK et al. Pulmonary and extrapulmonary complications of human rhinovirus infection in critically ill patients. J Clin Virol 2016; 77:85–91 [View Article][PubMed]
    [Google Scholar]
  6. To KKW, Yip CC, Yuen K-Y. Rhinovirus - From bench to bedside. J Formos Med Assoc 2017; 116:496–504 [View Article][PubMed]
    [Google Scholar]
  7. To KKW, Lu L, Fong CH, Wu AKL, Mok K-Y et al. Rhinovirus respiratory tract infection in hospitalized adult patients is associated with TH2 response irrespective of asthma. J Infect 2018; 76:465–474 [View Article][PubMed]
    [Google Scholar]
  8. Kumar N, Sharma S, Barua S, Tripathi BN, Rouse BT. Virological and immunological outcomes of coinfections. Clin Microbiol Rev 2018; 31: [View Article][PubMed]
    [Google Scholar]
  9. To KKW, Hung IF, Li IWS, Lee K-L, Koo C-K et al. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 2010; 50:850–859 [View Article][PubMed]
    [Google Scholar]
  10. Mosser AG, Vrtis R, Burchell L, Lee WM, Dick CR et al. Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues. Am J Respir Crit Care Med 2005; 171:645–651 [View Article][PubMed]
    [Google Scholar]
  11. To KKW, Lee K-C, Wong SSY, Sze K-H, Ke Y-H et al. Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia. Diagn Microbiol Infect Dis 2016; 85:249–254 [View Article][PubMed]
    [Google Scholar]
  12. Gentile DA, Fireman P, Skoner DP. Elevations of local leukotriene C4 levels during viral upper respiratory tract infections. Ann Allergy Asthma Immunol 2003; 91:270–274 [View Article][PubMed]
    [Google Scholar]
  13. Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 2013; 153:112–125 [View Article][PubMed]
    [Google Scholar]
  14. Tam VC, Quehenberger O, Oshansky CM, Suen R, Armando AM et al. Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell 2013; 154:213–227 [View Article][PubMed]
    [Google Scholar]
  15. Morrison J, Josset L, Tchitchek N, Chang J, Belser JA et al. H7N9 and other pathogenic avian influenza viruses elicit a three-pronged transcriptomic signature that is reminiscent of 1918 influenza virus and is associated with lethal outcome in mice. J Virol 2014; 88:10556–10568 [View Article][PubMed]
    [Google Scholar]
  16. Kosaraju R, Guesdon W, Crouch MJ, Teague HL, Sullivan EM et al. B cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection. J Immunol 2017; 198:4738–4752 [View Article][PubMed]
    [Google Scholar]
  17. Tanner LB, Chng C, Guan XL, Lei Z, Rozen SG et al. Lipidomics identifies a requirement for peroxisomal function during influenza virus replication. J Lipid Res 2014; 55:1357–1365 [View Article][PubMed]
    [Google Scholar]
  18. Roulin PS, Lotzerich M, Torta F, Tanner LB, van Kuppeveld FJ et al. Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface. Cell Host Microbe 2014; 16:677–690 [View Article][PubMed]
    [Google Scholar]
  19. Staring J, von Castelmur E, Blomen VA, van den Hengel LG, Brockmann M et al. PLA2G16 represents a switch between entry and clearance of Picornaviridae. Nature 2017; 541:412–416 [View Article][PubMed]
    [Google Scholar]
  20. Yuan S, Chu H, Chan JF, Ye Z-W, Wen L et al. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun 2019; 10:120 [View Article][PubMed]
    [Google Scholar]
  21. Zhang AJX, Zhu H, Chen Y, Li C, Li C et al. Prostaglandin E2-Mediated impairment of innate immune response to A(H1N1)pdm09 infection in Diet-Induced obese mice could be restored by paracetamol. J Infect Dis 2019; 219:795–807 [View Article][PubMed]
    [Google Scholar]
  22. Li C, Li C, Zhang AJ, To KKW, Lee AC et al. Avian influenza A H7N9 virus induces severe pneumonia in mice without prior adaptation and responds to a combination of zanamivir and COX-2 inhibitor. PLoS One 2014; 9:e107966 [View Article][PubMed]
    [Google Scholar]
  23. Chan JF, Yuan S, Kok KH, To KK-W, Chu H et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395:514–523 [View Article][PubMed]
    [Google Scholar]
  24. Zheng B, Chan KH, Zhang AJ, Zhou J, Chan CC et al. D225G mutation in hemagglutinin of pandemic influenza H1N1 (2009) virus enhances virulence in mice. Exp Biol Med 2010; 235:981–988 [View Article][PubMed]
    [Google Scholar]
  25. To KKW, Mok K-Y, Chan AS, Cheung NN, Wang P et al. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans. J Gen Virol 2016; 97:1807–1817 [View Article][PubMed]
    [Google Scholar]
  26. Dissanayake TK, Schauble S, Mirhakkak MH, Wu W-L, Ng AC-K et al. Comparative transcriptomic analysis of rhinovirus and influenza virus infection. Front Microbiol 2020; 11:1580 [View Article][PubMed]
    [Google Scholar]
  27. Zhao H, To KKW, Sze K-H, Yung TT, Bian M et al. A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2. Nat Commun 2020; 11:4252 [View Article][PubMed]
    [Google Scholar]
  28. Chu H, Chan JF-W, Yuen TT-T, Shuai H, Yuan S et al. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe 2020; 1:e14–e23 [View Article][PubMed]
    [Google Scholar]
  29. To KKW, Lau CC, Woo PC, Lau SK, Chan JF et al. Human H7N9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken H7N9 virus. Virol J 2016; 13:42 [View Article][PubMed]
    [Google Scholar]
  30. Yan B, Chu H, Yang D, Sze KH, Lai PM et al. Characterization of the lipidomic profile of human coronavirus-infected cells: implications for lipid metabolism remodeling upon coronavirus replication. Viruses 2019; 11:73 [View Article][PubMed]
    [Google Scholar]
  31. Burnum-Johnson KE, Kyle JE, Eisfeld AJ, Casey CP, Stratton KG et al. MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-OMICS profiling. Analyst 2017; 142:442–448 [View Article][PubMed]
    [Google Scholar]
  32. Silva LP, Lorenzi PL, Purwaha P, Yong V, Hawke DH et al. Measurement of DNA concentration as a normalization strategy for metabolomic data from adherent cell lines. Anal Chem 2013; 85:9536–9542 [View Article][PubMed]
    [Google Scholar]
  33. Yang Z, Hou JJ, Qi P, Yang M, Yan BP et al. Colon-derived uremic biomarkers induced by the acute toxicity of Kansui radix: A metabolomics study of rat plasma and intestinal contents by UPLC-QTOF-MS(E). J Chromatogr B Analyt Technol Biomed Life Sci 2016; 1026:193–203 [View Article][PubMed]
    [Google Scholar]
  34. Kind T, Liu KH, Lee DY, DeFelice B, Meissen JK et al. LipidBlast in silico tandem mass spectrometry database for lipid identification. Nat Methods 2013; 10:755–758 [View Article][PubMed]
    [Google Scholar]
  35. Tsugawa H, Cajka T, Kind T, Ma Y, Higgins B et al. MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis. Nat Methods 2015; 12:523–526 [View Article][PubMed]
    [Google Scholar]
  36. Chong J, Soufan O, Li C, Caraus I, Li S et al. MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res 2018; 46:W486–W494 [View Article][PubMed]
    [Google Scholar]
  37. Galindo-Prieto B, Eriksson L, Trygg J. Variable influence on projection (VIP) for orthogonal projections to latent structures (OPLS). J Chemom 2014; 28:623–632 [View Article]
    [Google Scholar]
  38. Zhu ZJ, Schultz AW, Wang J, Johnson CH, Yannone SM et al. Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database. Nat Protoc 2013; 8:451–460 [View Article][PubMed]
    [Google Scholar]
  39. Yan B, Deng Y, Hou J, Bi Q, Yang M et al. UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet. Mol Biosyst 2015; 11:486–496 [View Article][PubMed]
    [Google Scholar]
  40. To KK, Lu L, Yip CC, Poon RW, Fung AM et al. Additional molecular testing of saliva specimens improves the detection of respiratory viruses. Emerg Microbes Infect 2017; 6:e49 [View Article][PubMed]
    [Google Scholar]
  41. Chan JF, Yip CC, To KK-W, Tang TH, Wong SC et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel Real-Time reverse transcription-PCR Assay Validated In Vitro and with clinical specimens. J Clin Microbiol 2020; 58: [View Article][PubMed]
    [Google Scholar]
  42. Nguyen A, Guedan A, Mousnier A, Swieboda D, Zhang Q et al. Host lipidome analysis during rhinovirus replication in HBECs identifies potential therapeutic targets. J Lipid Res 2018; 59:1671–1684 [View Article][PubMed]
    [Google Scholar]
  43. Audi A, Soudani N, Dbaibo G, Zaraket H. Depletion of host and viral sphingomyelin impairs influenza virus infection. Front Microbiol 2020; 11:612 [View Article][PubMed]
    [Google Scholar]
  44. Tafesse FG, Sanyal S, Ashour J, Guimaraes CP, Hermansson M et al. Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. Proc Natl Acad Sci U S A 2013; 110:6406–6411 [View Article][PubMed]
    [Google Scholar]
  45. Aizaki H, Morikawa K, Fukasawa M, Hara H, Inoue Y et al. Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. J Virol 2008; 82:5715–5724 [View Article][PubMed]
    [Google Scholar]
  46. Miller ME, Adhikary S, Kolokoltsov AA, Davey RA. Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J Virol 2012; 86:7473–7483 [View Article][PubMed]
    [Google Scholar]
  47. Otsuki N, Sakata M, Saito K, Okamoto K, Mori Y et al. Both sphingomyelin and cholesterol in the host cell membrane are essential for rubella virus entry. J Virol 2018; 92: [View Article][PubMed]
    [Google Scholar]
  48. Pastenkos G, Miller JL, Pritchard SM, Nicola AV. Role of sphingomyelin in alphaherpesvirus entry. J Virol 2019; 93: [View Article][PubMed]
    [Google Scholar]
  49. Fernandez-Oliva A, Ortega-Gonzalez P, Risco C. Targeting host lipid flows: exploring new antiviral and antibiotic strategies. Cell Microbiol 2019; 21:e12996 [View Article][PubMed]
    [Google Scholar]
  50. Wu A, Mihaylova VT, Landry ML, Foxman EF. Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study. Lancet Microbe 2020; 1:e254–e262 [View Article][PubMed]
    [Google Scholar]
  51. Casalegno JS, Ottmann M, Duchamp MB, Escuret V, Billaud G et al. Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France. Clin Microbiol Infect 2010; 16:326–329 [View Article][PubMed]
    [Google Scholar]
  52. Song JW, Lam SM, Fan X, Cao WJ, Wang SY et al. Omics-Driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis. Cell Metab 2020; 32:188–202 [View Article][PubMed]
    [Google Scholar]
  53. Wang H, Yang P, Liu K, Guo F, Zhang Y et al. Sars coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res 2008; 18:290–301 [View Article][PubMed]
    [Google Scholar]
  54. Slotte JP. Biological functions of sphingomyelins. Prog Lipid Res 2013; 52:424–437 [View Article][PubMed]
    [Google Scholar]
  55. Schneider-Schaulies J, Schneider-Schaulies S. Sphingolipids in viral infection. Biol Chem 2015; 396:585–595 [View Article][PubMed]
    [Google Scholar]
  56. Weng L, Hirata Y, Arai M, Kohara M, Wakita T et al. Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner. J Virol 2010; 84:11761–11770 [View Article][PubMed]
    [Google Scholar]
  57. Soudani N, Hage-Sleiman R, Karam W, Dbaibo G, Zaraket H. Ceramide Suppresses Influenza A Virus Replication In Vitro. J Virol 2019; 93: [View Article][PubMed]
    [Google Scholar]
  58. Anjum F, Joshi K, Grinkina N, Gowda S, Cutaia M et al. Role of sphingomyelin synthesis in pulmonary endothelial cell cytoskeletal activation and endotoxin-induced lung injury. Am J Respir Cell Mol Biol 2012; 47:94–103 [View Article][PubMed]
    [Google Scholar]
  59. McVey MJ, Kim M, Tabuchi A, Srbely V, Japtok L et al. Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets. Am J Physiol Lung Cell Mol Physiol 2017; 312:L625–L637 [View Article][PubMed]
    [Google Scholar]
  60. Okuro RT, Machado MN, Casquilho NV, Jardim-Neto A, Roncally-Carvalho A et al. The role of sphingolipid metabolism disruption on lipopolysaccharide-induced lung injury in mice. Pulm Pharmacol Ther 2018; 50:100–110 [View Article][PubMed]
    [Google Scholar]
  61. Ramos I, Smith G, Ruf-Zamojski F, Martinez-Romero C, Fribourg M et al. Innate immune response to influenza virus at single-cell resolution in human epithelial cells revealed paracrine induction of interferon lambda 1. J Virol 2019; 93:e00559–19 [View Article][PubMed]
    [Google Scholar]
  62. Rajan D, McCracken CE, Kopleman HB, Kyu SY, Lee FE et al. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells. PLoS One 2014; 9:e114322 [View Article][PubMed]
    [Google Scholar]
  63. Aevermann BD, Pickett BE, Kumar S, Klem EB, Agnihothram S et al. A comprehensive collection of systems biology data characterizing the host response to viral infection. Sci Data 2014; 1:140033 [View Article][PubMed]
    [Google Scholar]
  64. Shen B, Yi X, Sun Y, Bi X, Du J et al. Proteomic and metabolomic characterization of COVID-19 patient sera. Cell 2020; 182:e1559–72 [View Article][PubMed]
    [Google Scholar]
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