Advertisement

The Role of Secreted Serine Proteases of the Host in Influenza Viral Pathogenesis

  • Hiroshi Kido
Chapter

Abstract

Influenza A virus (IAV) is one of the most common pathogens causing acute respiratory infections in humans of all age group. IAV infectivity depends on activation of the viral hemagglutinin by proteolytic enzymes of the host, among which secreted trypsin-type serine proteases play a prominent role. Proinflammatory cytokines induced in influenza virus infections upregulate production of the proteases and, thus, enhance virus replication, tissue damage, and metabolic disorders. Application of protease inhibitors counteracting these effects is therefore a promising therapeutic regimen against influenza.

Keywords

Influenza virus Sendai virus Trypsin-type serine proteases Cytokines Multiple organ failure 

Notes

Acknowledgment

Our studies were supported in part by grants-in-aid #16H05348 and the Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of Japan and by Health and Labour Sciences Research Grants (grant #12103307) from the Ministry of Health, Labour and Welfare of Japan.

References

  1. Beppu Y, Immamura Y, Tashiro M, Towatari T, Ariga H, Kido H. Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses. J Biochem. 1997;121:309–16.CrossRefPubMedGoogle Scholar
  2. Bersin RM, Stacpoole PW. Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am Heart J. 1997;134:841–55.CrossRefPubMedGoogle Scholar
  3. Böttcher E, Matrosovich T, Beyerle M, Klenk H-D, Garten W, Matrosovich M. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. J Virol. 2006;80:9896–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chaipan C, Kobasa D, Bertram S, Glowacka I, Steffen I, Tsegaye TS, Takeda M, Bugge TH, Kim S, Park Y, Marzi A, Pöhlmann S. Proteolytic activation of the 1918 influenza virus hemagglutinin. J Virol. 2009;83:3200–11.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chen Y, Shiota M, Ohuchi M, Towatari T, Tashiro M, Murakami M, Yano M, Yang B, Kido H. Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza viruses. Purification and characterization. Eur J Biochem. 2000;267:3189–97.CrossRefPubMedGoogle Scholar
  6. Dolorme L, Middleton PJ. Influenza A virus associated with acute encephalopathy. Am J Dis Child. 1979;133:822–4.Google Scholar
  7. Fujimoto S, Kobayashi M, Uemura O, Iwasa M, Ando T, Katoh T, Nakamura C, Maki N, Togari H, Wada Y. PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis. Lancet. 1998;352:873–5.CrossRefPubMedGoogle Scholar
  8. Gotoh B, Ogasawara T, Toyoda TM, Inocencio N, Hamaguchi M, Nagai Y. An endoprotease homologous to the blood clotting factor X as a determinant of viral tropism in chick embryo. EMBO J. 1990;9:4189–95.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hamilton BS, Whittaker GR. Cleavage activation of human-adapted influenza virus subtypes by kallikrein-related peptidases 5 and 12. J Biol Chem. 2013;288:17399–407.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hiyoshi M, Indalao IL, Yano M, Yamane K, Takahashi E, Kido H. Influenza A virus infection of vascular endothelial cells induces GSK-3β-mediated β-catenin degradation in adherens junctions, with a resultant increase in membrane permeability. Arch Virol. 2015;160:225–34.CrossRefPubMedGoogle Scholar
  11. Ichiyama T, Morishima T, Kajimoto M, Matsushige T, Matsubara T, Furukawa S. Matrix metalloprotease-9 and tissue inhibitors of metalloproteinases I in influenza-associated encephalopathy. Pediatr Infect Dis J. 2007;26:542–4.CrossRefPubMedGoogle Scholar
  12. Indalao IL, Sawabuchi T, Takahashi E, Kido H. IL-1β is a key cytokine that induces trypsin upregulation in the influenza-cytokine-trypsin cycle. Arch Virol. 2016;162:201–11.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kato M, Li J, Chuang JL, Chung DT. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007;15:992–1004.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Khoufache K, LeBouder F, Morello E, Laurent F, Riffault S, Andrade-Gordon P, Boullier S, Rousset P, Vergnolle N, Riteau B. Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-γ-dependent pathway. J Immunol. 2009;182:7795–802.CrossRefPubMedGoogle Scholar
  15. Kido H. Influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options. Proc Jpn Acad Ser B. 2015;91:351–68.CrossRefGoogle Scholar
  16. Kido H, Murakami M, Oba K, Chen Y, Towatari T. Cellular proteinases trigger the infectivity of influenza A and Sendai viruses. Mol Cells. 1999;9:235–44.PubMedGoogle Scholar
  17. Kido H, Okumura Y, Takahashi E, Pan H, Wang S, Chida J, Le TQ, Yano M. Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses. J Mol Genet Med. 2009;3:167–75.CrossRefGoogle Scholar
  18. Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Yao D, Yao M, Chida J, Yano M. Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure. Biochim Biophys Acta. 2012;1824:186–94.CrossRefPubMedGoogle Scholar
  19. Kido H, Okumura Y, Yamada H, Le TQ, Yano M. Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents. Curr Pharm Des. 2007;13:405–14.CrossRefPubMedGoogle Scholar
  20. Kido H, Yokogoshi Y, Sakai K, Tashiro M, Kishino Y, Fukutomi A, Katunuma N. Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein. J Biol Chem. 1992;267:13573–9.PubMedPubMedCentralGoogle Scholar
  21. Kim HM, Brandt CD, Arrobio JO, Murphy B, Chanock RM, Parrott RH. Influenza A and B virus infection in infants and young children during the years 1957-1976. Am J Epidemiol. 1979;109:464–79.CrossRefPubMedGoogle Scholar
  22. Klenk H-D, Garten W. Host cell proteases controlling virus pathogenicity. Trends Microbiol. 1994;2:39–43.CrossRefPubMedGoogle Scholar
  23. Klenk H-D, Rott R, Orlich M, Blödom J. Activation of influenza A viruses by trypsin treatment. Virology. 1975;68:426–39.CrossRefPubMedGoogle Scholar
  24. Kunzelmann K, Schreiber R, König J, Mall M. Ion transport induced by proteinase-activated receptors (PAR2) in colon and airways. Cell Biochem Biophys. 2002;4:31–9.Google Scholar
  25. Lazarowitz SG, Goldberg AR, Choppin PW. Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus: host cell activation of serum plasminogen. Virology. 1973;56:172–80.CrossRefPubMedGoogle Scholar
  26. Le TQ, Kawachi M, Yamada H, Shiota M, Okumura Y, Kido H. Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain. Biol Chem. 2006;387:467–75.PubMedGoogle Scholar
  27. Lipatov AS, Govorkova EA, Webby RJ, Ozaki H, Peiris M, Guan Y, Poon L, Webster RG. Influenza: emergence and control. J Virol. 2004;78:8951–9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Mooren HWD, Kramps JA, Franken C, Meijer CJLM, Dickmen JA. Localization of a low-molecular-weight bronchial protease inhibitor in the peripheral human lung. Thorax. 1983;38(3):180.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Mori I, Goshima F, Koshizuka T, Koide N, Sugiyama T, Yoshida T, Yokochi T, Nishiyama Y, Kimura Y. Differential activation of the c-Jun N-terminal kinase/stress-activated protein kinase and p38 mitogen-activated protein kinase signal transduction pathways in the mouse brain upon infection with neurovirulent influenza A virus. J Gen Virol. 2003;84:2401–8.CrossRefPubMedGoogle Scholar
  30. Murakami M, Towatari T, Ohuchi M, Shiota M, Akao M, Okumura Y, Parry MA, Kido H. Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus. Eur J Biochem. 2001;268:2847–55.CrossRefPubMedGoogle Scholar
  31. Nakayama T, Hirano K, Nishimura J, Takahashi S, Kanaide H. Mechanism of trypsin-induced endothelium-dependent vasorelaxation in the porcine coronary artery. Br J Pharmacol. 2001;134:815–26.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Nimmerjahn F, Dudziak D, Dirmeier U, Hobom G, Riedel A, Schlee M, Staudt LM, Rosenwald A, Behrends U, Bornkamm GW, Mautner J. Active NF-κB signaling is a prerequisite for influenza virus infection. J Gen Virol. 2004;85:2347–56.CrossRefPubMedGoogle Scholar
  33. Niu QX, Chen HQ, Chen ZY, Fu YL, Lin JL, He SH. Induction of inflammatory cytokine release from human umbilical vein endothelial cells by agonists of proteinase-activated receptor-2. Clin Exp Pharmacol Physiol. 2008;35:89–96.CrossRefPubMedGoogle Scholar
  34. Palmer ML, Lee SY, Maniak PJ, Carlson D, Fahrenkrug SC, O’Grady SM. Protease-activated receptor regulation of Cl- secretion in Calu-3 cells requires prostaglandin release and CFTR activation. Am J Physiol Cell Physiol. 2006;290:C1189–C98.CrossRefPubMedGoogle Scholar
  35. Pan H, Yamada H, Chida J, Wang S, Yano M, Yao M, Zhu J, Kido H. Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis. Cardiovasc Res. 2011;89:595–603.CrossRefPubMedGoogle Scholar
  36. Puchelle EJ, Hinnraski J, Tournier JM, Adnet JJ. Ultrastructural localization of bronchial inhibitor in human airways using protein A-gold technique. Biol Cell. 1985;55:151–4.CrossRefPubMedGoogle Scholar
  37. Santoro MG, Rossi A, Amici C. NF-κB and virus infection: who controls whom. EMBO J. 2003;22:2552–60.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Sato M, Yoshida S, Iida K, Tomozawa T, Kido H, Yamashita M. A novel influenza A virus activating enzyme from porcine lung: purification and characterization. Biol Chem. 2003;384:219–27.Google Scholar
  39. Scheiblauer H, Reinacher M, Tashiro M, Rott R. Interactions between bacteria and influenza A virus in the development of influenza pneumonia. J Infect Dis. 1992;166:783–91.CrossRefPubMedGoogle Scholar
  40. Spraque AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009;78:539–52.CrossRefGoogle Scholar
  41. Tashiro M, Ciborowski P, Klenk H-D, Pulverer G, Rott R. Role of staphylococcus protease in the development of influenza pneumonia. Nature. 1987;352:536–7.CrossRefGoogle Scholar
  42. Tashiro M, Yokogoshi Y, Tobita K, Seto JT, Rott R, Kido H. Tryptase Clara an activating protease for Sendai virus in rat lungs, is involved in pneumopathogenicity. J Virol. 1992;22:7211–6.Google Scholar
  43. Towatari T, Ide M, Ohba K, Chiba Y, Murakami M, Shiota M, Kawachi M, Yamada H, Kido H. Identification of ectopic anionic trypsin I in rat lungs potentiating pneumotropic virus infectivity and increased enzyme level after virus infection. Eur J Biochem. 2002;269:2613–21.CrossRefPubMedGoogle Scholar
  44. Wang S, Le TQ, Kurihara N, Chida J, Cisse Y, Yano M, Kido H. Influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza. J Infect Dis. 2010;202:991–1001.CrossRefPubMedGoogle Scholar
  45. Yamane K, Indalao IL, Chida J, Yamamoto Y, Hanawa M, Kido H. Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4 inhibitor, as a potential therapeutic agent for metabolic disorders and multiorgan failure in severe influenza. PLoS One. 2014;9:e98032.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Yao D, Chen Y, Kuwajima M, Shiota M, Kido H. Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion of the murine brain by a pneumotropic influenza A virus: implications for influenza-associated encephalopathy. Biol Chem. 2004;385:487–92.CrossRefPubMedGoogle Scholar
  47. Yasuoka S, Ohnishi T, Kawano S, Tsuchihashi S, Ogawara M, Masuda K, Yamaoka K, Takahashi M, Sano T. Purification, characterization, and localization of a novel trypsin-like protease found in the human airway. Am J Respir Cell Mol Biol. 1997;16:300–8.CrossRefPubMedGoogle Scholar
  48. Zhirnov OP, Golyando PB, Ovcharenko AV. Replication of influenza B virus in chicken embryos is suppressed by exogenous aprotinin. Arch Virol. 1994;135:209–16.CrossRefPubMedGoogle Scholar
  49. Zhirnov OP, Klenk H-D, Wright PF. Aprotinin and similar protease inhibitors as drugs against influenza. Antivir Res. 2011;92:27–36.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Enzyme Chemistry, Institute for Enzyme ResearchTokushima UniversityTokushimaJapan

Personalised recommendations