Skip to main content
SpringerLink
Log in

Virus and Autophagy: Enemies or Allies

  • Chapter
  • First Online:
Autophagy in Health and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 644 Accesses

Abstract

Viral infection is one of the several stimuli which trigger autophagy, a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. This process also plays a housekeeping role in removing misfolded or aggregated proteins and clearing damaged organelles. Virus-induced autophagy has a dual role since it may be beneficial to the host by eliminating intracellular pathogens or it may benefit some viruses, which have developed strategies to directly or indirectly subvert autophagy in order to promote different stages of the viral life cycle. The upregulation of both oxidative and endoplasmic reticulum stresses has been reported as a means by which virus-induced pathways trigger autophagy. In this chapter the relationships between autophagy and viral infection are considered.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
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 169.99
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. Galluzzi L, Pietrocola F, Levine B, Kroemer G. Metabolic control of autophagy. Cell. 2014;159:1263–76.

    Article  CAS  Google Scholar 

  2. Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14:759–74.

    Article  CAS  Google Scholar 

  3. Chiramel AI, Brady NR, Bartenschlager R. Divergent roles of autophagy in virus infection. Cells. 2013;2:83–104.

    Article  Google Scholar 

  4. Paulus GL, Xavier RJ. Autophagy and checkpoints for intracellular pathogen defense. Curr Opin Gastroenterol. 2015;31:14–23.

    Article  CAS  Google Scholar 

  5. Joubert PE, Werneke S, de la Calle C, Guivel-Benhassine F, Giodini A, Peduto L, Levine B, Schwartz O, Lenschow D, Albert ML. Chikungunya-induced cell death is limited by ER and oxidative stress-induced autophagy. Autophagy. 2012;8:1261–3.

    Article  CAS  Google Scholar 

  6. Joubert PE, Meiffren G, Grégoire IP, Pontini G, Richetta C, Flacher M, Azocar O, Vidalain PO, Vidal M, Lotteau V, Codogno P, Rabourdin-Combe C, Faure M. Autophagy induction by the pathogen receptor CD46. Cell Host Microbe. 2009;6:354–66.

    Article  Google Scholar 

  7. Denizot M, Varbanov M, Espert L, Robert-Hebmann V, Sagnier S, Garcia E, Curriu M, Mamoun R, Blanco J, Biard-Piechaczyk M. HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells. Autophagy. 2008;4:998–1008.

    Article  CAS  Google Scholar 

  8. Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest. 2006;116:2161–72.

    Article  CAS  Google Scholar 

  9. Mikula I Jr, Pastoreková S, Mikula I Sr. Toll-like receptors in immune response to the viral infections. Acta Virol. 2010;54:231–45.

    Article  CAS  Google Scholar 

  10. Loo YM, Gale M Jr. Immune signaling by RIG-I-like receptors. Immunity. 2011;34:680–92.

    Article  CAS  Google Scholar 

  11. Fensteri V, Sen GC. Interferons and viral infections. Biofactors. 2009;35:14–20.

    Article  Google Scholar 

  12. Sadler AJ, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol. 2008;8:559–68.

    Article  CAS  Google Scholar 

  13. Gorbea C, Makar KA, Pauschinger M, Pratt G, Bersola JL, Varela J, David RM, Banks L, Huang CH, Li H, Schultheiss HP, Towbin JA, Vallejo JG, Bowles NE. A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy. J Biol Chem. 2010;285:23208–23.

    Article  CAS  Google Scholar 

  14. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science. 2007;315:1398–401.

    Article  CAS  Google Scholar 

  15. Into T, Inomata M, Takayama E, Takigawa T. Autophagy in regulation of Toll-like receptor signaling. Cell Signal. 2012;24:1150–62.

    Article  CAS  Google Scholar 

  16. Delgado MA, Deretic V. Toll-like receptors in control of immunological autophagy. Cell Death Differ. 2009;16:976–83.

    Article  CAS  Google Scholar 

  17. Shi CS, Kehrl JH. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J Biol Chem. 2008;283:33175–82.

    Article  CAS  Google Scholar 

  18. Lippai M, Lőw P. The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. Biomed Res Int. 2014;2014:832704.

    Article  Google Scholar 

  19. Orvedahl A, MacPherson S, Sumpter R Jr, Talloczy Z, Zou Z, Levine B. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe. 2010;7:115–27.

    Article  CAS  Google Scholar 

  20. B’chir W, Maurin AC, Carraro V, Averous J, Jousse C, Muranishi Y, Parry L, Stepien G, Fafournoux P, Bruhat A. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 2013;41:7683–99.

    Article  Google Scholar 

  21. Martinon F. The endoplasmic reticulum: a sensor of cellular stress that modulates immune responses. Microbes Infect. 2012;14:1293–300.

    Article  CAS  Google Scholar 

  22. Gade P, Ramachandran G, Maachani UB, Rizzo MA, Okada T, Prywes R, Cross AS, Mori K, Kalvakolanu DV. An IFN-γ-stimulated ATF6-C/EBP-β-signaling pathway critical for the expression of death associated protein kinase 1 and induction of autophagy. Proc Natl Acad Sci U S A. 2012;109:10316–21.

    Article  CAS  Google Scholar 

  23. Ke PY, Chen SS. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest. 2011;121:37–56.

    Article  CAS  Google Scholar 

  24. Mohl BP, Tedbury PR, Griffin S, Harris M. Hepatitis C virus-induced autophagy is independent of the unfolded protein response. J Virol. 2012;86:10724–32.

    Article  CAS  Google Scholar 

  25. McLean JE, Wudzinska A, Datan E, Quaglino D, Zakeri Z. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J Biol Chem. 2011;286:22147–59.

    Article  CAS  Google Scholar 

  26. Carpenter JE, Jackson W, Benetti L, Grose C. Autophagosome formation during varicella zoster virus infection following endoplasmic reticulum stress and the unfolded protein response. J Virol. 2011;85:9414–24.

    Article  CAS  Google Scholar 

  27. Lee J, Giordano S, Zhang J. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441:523–40.

    Article  CAS  Google Scholar 

  28. Kosmider B, Messier EM, Janssen WJ, Nahreini P, Wang J, Hartshorn KL, Mason RJ. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir Res. 2012;13:43.

    Article  CAS  Google Scholar 

  29. Olagnier D, Peri S, Steel C, van Montfoort N, Chiang C, Beljanski V, Slifker M, He Z, Nichols CN, Lin R, Balachandran S, Hiscott J. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog. 2014;10:e1004566.

    Article  Google Scholar 

  30. Schaedler S, Krause J, Himmelsbach K, Carvajal-Yepes M, Lieder F, Klingel K, Nassal M, Weiss TS, Werner S, Hildt E. Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2. J Biol Chem. 2010;285:41074–86.

    Article  CAS  Google Scholar 

  31. Munz C. Antigen processing by macroautophagy for MHC presentation. Front Immunol. 2011;2:42.

    Article  Google Scholar 

  32. Leung CS, Taylor GS. Nuclear shelter: the influence of subcellular location on the processing of antigens by macroautophagy. Autophagy. 2010;6:510–1.

    Article  Google Scholar 

  33. Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, Tuschl T, Münz C. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science. 2005;307:593–6.

    Article  CAS  Google Scholar 

  34. English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippé R, Desjardins M. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol. 2009;10:480–7.

    Article  CAS  Google Scholar 

  35. Miller S, Krijnse-Locker J. Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol. 2008;6:363–74.

    Article  CAS  Google Scholar 

  36. Schlegel A, Giddings TH Jr, Ladinsky MS, Kirkegaard K. Cellular origin and ultrastructure of membranes induced during poliovirus infection. J Virol. 1996;70:6576–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Huang SC, Chang CL, Wang PS, Tsai Y, Liu HS. Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. J Med Virol. 2009;81:1241–52.

    Article  CAS  Google Scholar 

  38. O’Donnell V, Pacheco JM, LaRocco M, Burrage T, Jackson W, Rodriguez LL, Borca MV, Baxt B. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Virology. 2011;410:142–50.

    Article  Google Scholar 

  39. Granato M, Santarelli R, Farina A, Gonnella R, Lotti LV, Faggioni A, Cirone M. Epstein-barr virus blocks the autophagic flux and appropriates the autophagic machinery to enhance viral replication. J Virol. 2014;88:12715–26.

    Article  Google Scholar 

  40. Wen HJ, Yang Z, Zhou Y, Wood C. Enhancement of autophagy during lytic replication by the Kaposi’s sarcoma-associated herpesvirus replication and transcription activator. J Virol. 2010;84:7448–58.

    Article  CAS  Google Scholar 

  41. Grégoire IP, Richetta C, Meyniel-Schicklin L, Borel S, Pradezynski F, Diaz O, Deloire A, Azocar O, Baguet J, Le Breton M, Mangeot PE, Navratil V, Joubert PE, Flacher M, Vidalain PO, André P, Lotteau V, Biard-Piechaczyk M, Rabourdin-Combe C, Faure M. IRGM is a common target of RNA viruses that subvert the autophagy network. PLoS Pathog. 2011;7:e1002422.

    Article  Google Scholar 

  42. Wang X, Hou L, Du J, Zhou L, Ge X, Guo X, Yang H. Capsid, membrane and NS3 are the major viral proteins involved in autophagy induced by Japanese encephalitis virus. Vet Microbiol. 2015;178:217–29.

    Article  CAS  Google Scholar 

  43. Li J, Liu Y, Wang Z, Liu K, Wang Y, Liu J, Ding H, Yuan Z. Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment. J Virol. 2011;85:6319–33.

    Article  CAS  Google Scholar 

  44. Jackson WT, Giddings TH Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 2005;3:e156.

    Article  Google Scholar 

  45. Fliss PM, Jowers TP, Brinkmann MM, Holstermann B, Mack C, Dickinson P, Hohenberg H, Ghazal P, Brune W. Viral mediated redirection of NEMO/IKKgamma to autophagosomes curtails the inflammatory cascade. PLoS Pathog. 2012;8:e1002517.

    Article  CAS  Google Scholar 

  46. Green AM, Beatty PR, Hadjilaou A, Harris E. Innate immunity to dengue virus infection and subversion of antiviral responses. J Mol Biol. 2014;426:1148–60.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Funding: This work was supported by project grants GRUPIN14-071 and GRUPIN14-099 from PCTI (Principado de Asturias) and FEDER funds (EU).

Author information

Authors and Affiliations

  1. Servicio de Microbiología, Hospital Universitario Central de Asturias, Oviedo, Spain

    José A. Boga, Zulema Pérez-Martínez & Marta E. Alvarez-Argüelles

  2. Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain

    José A. Boga, Zulema Pérez-Martínez, Ana Coto-Montes & Marta E. Alvarez-Argüelles

  3. Departamento de Morfología y Biología Celular, Universidad de Oviedo, Oviedo, Spain

    Ana Coto-Montes

  4. Department of Cellular & Structural Biology, UT Health Science Center at San Antonio, San Antonio, TX, USA

    Russel J. Reiter

Authors
  1. José A. Boga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zulema Pérez-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Coto-Montes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marta E. Alvarez-Argüelles
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Russel J. Reiter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José A. Boga .

Editor information

Editors and Affiliations

  1. Ottawa, ON, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Boga, J.A., Pérez-Martínez, Z., Coto-Montes, A., Alvarez-Argüelles, M.E., Reiter, R.J. (2018). Virus and Autophagy: Enemies or Allies. In: Turksen, K. (eds) Autophagy in Health and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98146-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation