Skip to main content
SpringerLink
Log in

Systems Biology of Influenza: Understanding Multidimensional Interactions for Personalized Prevention and Treatment

  • Protocol
  • First Online:
Book cover Systems Biology in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 662))

Abstract

Influenza virus infection is a public health threat worldwide. It is urgent to develop effective methods and tools for the prevention and treatment of influenza. Influenza vaccines have significant immune response variability across the population. Most of the current circulating strains of influenza A virus are resistant to anti-influenza drugs. It is necessary to understand how genetic variants affect immune responses, especially responses to the HA and NA transmembrane glycoproteins. The elucidation of the underlying mechanisms can help identify patient subgroups for effective prevention and treatment. New personalized vaccines, adjuvants, and drugs may result from the understanding of interactions of host genetic, environmental, and other factors. The systems biology approach is to simulate and model large networks of the interacting components, which can be excellent targets for antiviral therapies. The elucidation of host–influenza interactions may provide an integrative view of virus infection and host responses. Understanding the host–influenza–drug interactions may contribute to optimal drug combination therapies. Insight of the host–influenza–vaccine interactions, especially the immunogenetics of vaccine response, may lead to the development of better vaccines. Systemic studies of host–virus–vaccine–drug–environment interactions will enable predictive models for therapeutic responses and the development of individualized therapeutic strategies. A database containing such information on personalized and systems medicine for influenza is available at http://flu.pharmtao.com.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Center for Disease Control and Prevention (CDC). Available at: http://www.cdc.gov/flu/about/disease/index.htm. Accessed July 2009

  2. http://flu.gov. Accessed July 2009

  3. World Health Organization (WHO). Available at: http://www.who.int/csr/disease/avian_influenza/phase/en/index.html. Accessed July 2009

  4. Memoli MJ, Morens DM, Taubenberger JK (2008) Pandemic and seasonal influenza: therapeutic challenges. Drug Discov Today 13:590–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brady MT (2006) Immunization recommendations for children with metabolic disorders: more data would help. Pediatrics 118:810–813

    Article  PubMed  Google Scholar 

  6. Yan Q (2008) Pharmacogenomics in drug discovery and development. Preface. Methods Mol Biol 448:v–vii

    PubMed  Google Scholar 

  7. Yan Q (2005) Pharmacogenomics and systems biology of membrane transporters. Mol Biotechnol 29:75–88

    Article  CAS  PubMed  Google Scholar 

  8. Poland GA, Ovsyannikova IG, Jacobson RM (2009) Application of pharmacogenomics to vaccines. Pharmacogenomics 10:837–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lambkin R, Novelli P, Oxford J et al (2004) Human genetics and responses to influenza vaccination: clinical implications. Am J Pharmacogenomics 4:293–298

    Article  CAS  PubMed  Google Scholar 

  10. Forst CV (2006) Host-pathogen systems biology. Drug Discov Today 11:220–227

    Article  CAS  PubMed  Google Scholar 

  11. Damm EM, Pelkmans L (2006) Systems biology of virus entry in mammalian cells. Cell Microbiol 8:1219–1227

    Article  CAS  PubMed  Google Scholar 

  12. Wong JP, Christopher ME, Viswanathan S et al (2009) Activation of toll-like receptor signaling pathway for protection against influenza virus infection. Vaccine 27:3481–3483

    Article  CAS  PubMed  Google Scholar 

  13. Min JY, Krug RM (2006) The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2′–5′ oligo (A) synthetase/RNase L pathway. Proc Natl Acad Sci USA 103:7100–7105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Krug RM, Lamb RA (2001) Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  15. Noah DL, Twu KY, Krug RM (2003) Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3′ end processing of cellular pre-mRNAS. Virology 307:386–395

    Article  CAS  PubMed  Google Scholar 

  16. Chen Z, Li Y, Krug RM (1999) Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J 18:2273–2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Donelan NR, Basler CF, Garcia-Sastre A (2003) A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice. J Virol 77:13257–13266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li S, Min JY, Krug RM et al (2006) Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 349:13–21

    Article  CAS  PubMed  Google Scholar 

  19. Ehrhardt C, Wolff T, Pleschka S et al (2007) Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J Virol 81:3058–3067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu Y, Zhang G, Li Y et al (2008) Inhibition of highly pathogenic avian H5N1 influenza virus replication by RNA oligonucleotides targeting NS1 gene. Biochem Biophys Res Commun 365:369–374

    Article  CAS  PubMed  Google Scholar 

  21. Hui EK, Barman S, Tang DH, France B, Nayak DP (2006) YRKL sequence of influenza virus M1 functions as the L domain motif and interacts with VPS28 and Cdc42. J Virol 80:2291–2308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nencioni L, Iuvara A, Aquilano K et al (2003) Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2. FASEB J 17:758–760

    CAS  PubMed  Google Scholar 

  23. Nencioni L, De Chiara G, Sgarbanti R et al (2009) Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication. J Biol Chem 284:16004–16015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Akaike T, Ando M, Oda T et al (1990) Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J Clin Invest 85:739–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xie D, Bai H, Liu L et al (2009) Apoptosis of lymphocytes and monocytes infected with influenza virus might be the mechanism of combating virus and causing secondary infection by influenza. Int Immunol 21:1251–1262

    Article  CAS  PubMed  Google Scholar 

  26. Morris SJ, Smith H, Sweet C (2002) Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role. Arch Virol 147:961–979

    Article  CAS  PubMed  Google Scholar 

  27. Rossman JS, Lamb RA (2009) Autophagy, apoptosis, and the influenza virus M2 protein. Cell Host Microbe 6:299–300

    Article  CAS  PubMed  Google Scholar 

  28. Chanturiya AN, Basanez G, Schubert U et al (2004) PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes. J Virol 78:6304–6312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zamarin D, Garcia-Sastre A, Xiao X et al (2005) Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog 1:e4

    Article  PubMed  PubMed Central  Google Scholar 

  30. Stasakova J, Ferko B, Kittel C et al (2005) Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1beta and 18. J Gen Virol 86:185–195

    Article  CAS  PubMed  Google Scholar 

  31. Zhou J, Law HK, Cheung CY et al (2006) Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian influenza virus-infected macrophages. J Infect Dis 193:945–953

    Article  CAS  PubMed  Google Scholar 

  32. Lin C, Zimmer SG, Lu Z et al (2001) The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis. Virology 287:202–213

    Article  CAS  PubMed  Google Scholar 

  33. Numajiri A, Mibayashi M, Nagata K (2006) Stimulus-dependent and domain-dependent cell death acceleration by an IFN-inducible protein, human MxA. J Interferon Cytokine Res 26:214–219

    Article  CAS  PubMed  Google Scholar 

  34. Mibayashi M, Nakad K, Nagata K (2002) Promoted cell death of cells expressing human MxA by influenza virus infection. Microbiol Immunol 46:29–36

    Article  CAS  PubMed  Google Scholar 

  35. Turan K, Mibayashi M, Sugiyama K et al (2004) Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res 32:643–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Arndt U, Wennemuth G, Barth P et al (2002) Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection. J Virol 76:9298–9306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mao H, Tu W, Qin G et al (2009) Influenza virus directly infects human natural killer cells and induces cell apoptosis. J Virol 83:9215–9222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hartshorn KL, White MR, Mogues T et al (2003) Lung and salivary scavenger receptor glycoprotein-340 contribute to the host defense against influenza A viruses. Am J Physiol Lung Cell Mol Physiol 285:L1066–L1076

    Article  CAS  PubMed  Google Scholar 

  39. Guillot L, Le Goffic R, Bloch S et al (2005) Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 280:5571–5580

    Article  CAS  PubMed  Google Scholar 

  40. Nakamura H, Tamura S, Watanabe I et al (2002) Enhanced resistancy of thioredoxin-transgenic mice against influenza virus-induced pneumonia. Immunol Lett 82:165–170

    Article  CAS  PubMed  Google Scholar 

  41. Masuyama T, Matsuo M, Ichimaru T et al (2002) Possible contribution of interferon-alpha to febrile seizures in influenza. Pediatr Neurol 27:289–292

    Article  PubMed  Google Scholar 

  42. Veckman V, Osterlund P, Fagerlund R et al (2006) TNF-alpha and IFN-alpha enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells. Virology 345:96–104

    Article  CAS  PubMed  Google Scholar 

  43. Bernasconi D, Amici C, La Frazia S et al (2005) The IkappaB kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells. J Biol Chem 280:24127–24134

    Article  CAS  PubMed  Google Scholar 

  44. Sun J, Madan R, Karp CL et al (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15:277–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Boon AC, de Mutsert G, Graus YM et al (2002) The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype. J Virol 76:582–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. McGill J, Heusel JW, Legge KL (2009) Innate immune control and regulation of influenza virus infections. J Leukoc Biol 86:803–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Achdout H, Arnon TI, Markel G et al (2003) Enhanced recognition of human NK receptors after influenza virus infection. J Immunol 171:915–923

    Article  CAS  PubMed  Google Scholar 

  48. White M, Kingma P, Tecle T et al (2008) Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus. J Immunol 181:7936–7943

    Article  CAS  PubMed  Google Scholar 

  49. Hartshorn KL, White MR, Tecle T et al (2006) Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D. J Immunol 176:6962–6972

    Article  CAS  PubMed  Google Scholar 

  50. White MR, Crouch E, Vesona J et al (2005) Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am J Physiol Lung Cell Mol Physiol 289:L606–L616

    Article  CAS  PubMed  Google Scholar 

  51. Nguyen JT, Hoopes JD, Smee DF et al (2009) Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob Agents Chemother 53:4115–4126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ilyushina NA, Hay A, Yilmaz N et al (2008) Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 52:3889–3897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li CY, Yu Q, Ye ZQ et al (2007) A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir. Cell Res 17:357–362

    Article  CAS  PubMed  Google Scholar 

  54. Tang YW, Li H, Wu H et al (2007) Host single-nucleotide polymorphisms and altered responses to inactivated influenza vaccine. J Infect Dis 196:1021–1025

    Article  CAS  PubMed  Google Scholar 

  55. Carroll DN, Carroll DG (2009) Fatal intracranial bleed potentially due to a warfarin and influenza vaccine interaction. Ann Pharmacother 43:754–760

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. PharmTao, Santa Clara, CA, USA

    Qing Yan

Authors
  1. Qing Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing Yan .

Editor information

Editors and Affiliations

  1. PharmTao, Santa Clara, California, USA

    Qing Yan

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Yan, Q. (2010). Systems Biology of Influenza: Understanding Multidimensional Interactions for Personalized Prevention and Treatment. In: Yan, Q. (eds) Systems Biology in Drug Discovery and Development. Methods in Molecular Biology, vol 662. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-800-3_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-800-3_14

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-799-0

  • Online ISBN: 978-1-60761-800-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation