Skip to main content
SpringerLink
Log in
Book cover

Autophagy in Infection and Immunity pp 267–285Cite as

Autophagy in Mammalian Antiviral Immunity

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 335))

Abstract

Autophagy plays diverse roles in cellular adaptation to stress and promotes vital housekeeping functions by recycling unused or damaged organelles and proteins. As an innate immune defense pathway, autophagy also protects against infection with diverse pathogens, including viruses. Autophagy combats infections with both RNA and DNA viruses, and may function by degrading viral components, by promoting the survival of virally infected cells, and/or by activating innate and adaptive immunity. Viruses have evolved counter-mechanisms to evade host autophagy in order to promote their own survival. This chapter will highlight recent advances and unanswered questions relating to autophagy in mammalian antiviral immunity.

This is a preview of subscription content, 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   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

References

  • Alexander DE, Ward SL, Mizushima N, Levine B, Leib DA (2007) Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. J Virol 81:12128–12134

    Article  CAS  PubMed  Google Scholar 

  • Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS (2008) Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE 3:e2906

    Article  PubMed  Google Scholar 

  • Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319:921–926

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi A, Dorward D, Pierce SK (2008) The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 28:799–809

    Article  CAS  PubMed  Google Scholar 

  • Chaumorcel M, Souquère S, Pierron G, Codogno P, Esclatine A (2008) Human cytomegalovirus controls a new autophagy-dependent cellular antiviral defense mechanism. Autophagy 4:46–53

    CAS  PubMed  Google Scholar 

  • Chou J, Kern ER, Whitley RJ, Roizman B (1990) Mapping of herpes simplex virus-1 neurovirulence to γ134.5, a gene nonessential for growth in culture. Science 250:1262–1266

    Article  CAS  PubMed  Google Scholar 

  • Chou J, Roizman B (1994) Herpes simplex virus 1 γ134.5 gene function, which blocks the host response to infection, maps in the homologous domain of the genes expressed during growth arrest and DNA damage. Proc Natl Acad Sci USA 91:5247–5251

    Article  CAS  PubMed  Google Scholar 

  • DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL (2002) Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J Infect Dis 186:1547–1557

    Article  PubMed  Google Scholar 

  • Delgado MA, Elmaoued RA, Davis AS, Kyei G, Deretic V (2008) Toll-like receptors control autophagy. Embo J 27:1110–1121

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M (2006) Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest 116:2161–2172

    Article  CAS  PubMed  Google Scholar 

  • Finlay BB, McFadden G (2006) Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124:767–782

    Article  CAS  PubMed  Google Scholar 

  • Gandhi MK, Khanna R (2004) Human cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 4:725–738

    Article  CAS  PubMed  Google Scholar 

  • Geiger KD, Nash TC, Sawyer S, Krahl T, Patstone G, Reed JC, Krajewski S, Dalton D, Buchmeier MJ, Sarvetnick N (1997) Interferon-gamma protects against herpes simplex virus type 1-mediated neuronal death. Virology 238:189–197

    Article  CAS  PubMed  Google Scholar 

  • He B, Chou J, Liebermann DA, Hoffman B, Roizman B (1996) The carboxyl terminus of the murine MyD116 gene substitutes for the corresponding domain of the γ134.5 gene of herpes simplex virus to preclude the premature shutoff of total protein synthesis in infected human cells. J Virol 70:84–90

    CAS  PubMed  Google Scholar 

  • He B, Gross M, Roizman B (1997) The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U SA 94:843–848

    Article  CAS  Google Scholar 

  • He C, Orvedahl A (2007) 2007 keystone symposium on autophagy in health and disease. Autophagy 3:527–536

    PubMed  Google Scholar 

  • Johnston C, Jiang W, Chu T, Levine B (2001) Identification of genes involved in the host response to neurovirulent alphavirus infection. J Virol 75:10431–10445

    Article  CAS  PubMed  Google Scholar 

  • Ku B, Woo JS, Liang C, Lee KH, Hong HS, Kim KS, Jung JU, Oh BH (2008) Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine γ-herpesvirus 68. PLoS Pathog 4:e25

    Article  PubMed  Google Scholar 

  • Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–1401

    Article  CAS  PubMed  Google Scholar 

  • Levine B (2002) Apoptosis in viral infections of neurons: a protective or pathologic host response? Curr Top Microbiol Immunol 265: 95–118

    CAS  PubMed  Google Scholar 

  • Levine B (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120:159–162

    CAS  PubMed  Google Scholar 

  • Levine B (2007) Cell biology: autophagy and cancer. Nature 446:745–747

    Article  CAS  PubMed  Google Scholar 

  • Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7:767–777

    Article  CAS  PubMed  Google Scholar 

  • Levine B, Goldman JE, Jiang HH, Griffin DE, Hardwick JM (1996) Bc1-2 protects mice against fatal alphavirus encephalitis. Proc Natl Acad Sci USA 93:4810–4815

    Article  CAS  PubMed  Google Scholar 

  • Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42

    Article  CAS  PubMed  Google Scholar 

  • Levine B, Sinha S, Kroemer G (2008) Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4:600–606

    CAS  PubMed  Google Scholar 

  • Lewis J, Oyler GA, Ueno K, Fannjiang YR, Chau BN, Vornov J, Korsmeyer SJ, Zou S, Hardwick JM (1999) Inhibition of virus-induced neuronal apoptosis by Bax. Nat Med 5:832–835

    Article  CAS  PubMed  Google Scholar 

  • Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH, Jung JU (2006) Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 8:688–699

    Article  CAS  PubMed  Google Scholar 

  • Liang XH, Goldman JE, Jiang HH, Levine B (1999) Resistance of interleukin-1β-deficient mice to fatal Sindbis virus encephalitis. J Virol 73:2563–2567

    CAS  PubMed  Google Scholar 

  • Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman J, Berry G, Herman B, Levine B (1998) Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J Virol 72:8586.

    CAS  PubMed  Google Scholar 

  • Liu Y, Schiff M, Czymmek K, Tallóczy Z, Levine B, Dinesh-Kumar SP (2005) Autophagy regulates programmed cell death during the plant innate immune response. Cell 121:567–577

    Article  CAS  PubMed  Google Scholar 

  • Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752

    Article  CAS  PubMed  Google Scholar 

  • Markovitz NS, Baunoch D, Roizman B (1997) The range and distribution of murine central nervous system cells infected with the γ134.5− mutant of herpes simplex virus 1. J Virol 71:5560–5569

    CAS  PubMed  Google Scholar 

  • Mettenleiter TC, Klupp BG, Granzow H (2006) Herpesvirus assembly: a tale of two membranes. Curr Opin Microbiol 9:423–429

    Article  CAS  PubMed  Google Scholar 

  • Mohr I, Sternberg D, Ward S, Leib D, Mulvey M, Gluzman Y (2001) A herpes simplex virus type 1 γ34.5 second-site suppressor mutant that exhibits enhanced growth in cultured glioblastoma cells is severely attenuated in animals. J Virol 75:5189–5196

    Article  CAS  PubMed  Google Scholar 

  • Nakashima A, Tanaka N, Tamai K, Kyuuma M, Ishikawa Y, Sato H, Yoshimori T, Saito S, Sugamura K (2006) Survival of parvovirus B19-infected cells by cellular autophagy. Virology 349:254–263

    Article  CAS  PubMed  Google Scholar 

  • Nava VE, Rosen A, Veliuona MA, Clem RJ, Levine B, Hardwick JM (1998) Sindbis virus induces apoptosis through a caspase-dependent, CrmA-sensitive pathway. J Virol 72:452–459

    CAS  PubMed  Google Scholar 

  • Orvedahl A, Alexander D, Tallóczy Z, Sun Q, Wei Y, Zhang W, Burns D, Leib DA, Levine B (2007) HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1:23–35

    Article  CAS  PubMed  Google Scholar 

  • Orvedahl A, Levine B (2008) Autophagy and viral neurovirulence. Cell Microbiol 10:1747–1756

    Article  CAS  PubMed  Google Scholar 

  • Orvedahl A, Levine B (2009) Eating the enemy within: autophagy in infectious diseases. Cell Death Differ 16:57–69

    Article  CAS  PubMed  Google Scholar 

  • Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939

    Article  CAS  PubMed  Google Scholar 

  • Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y et al (2003) Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 112:1809–1820

    CAS  PubMed  Google Scholar 

  • Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M et al (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 456:264–268

    Article  CAS  PubMed  Google Scholar 

  • Schmid D, Pypaert M, Munz C (2007) Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26:79–92

    Article  CAS  PubMed  Google Scholar 

  • Shi CS, Kehrl JH (2008) MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J Biol Chem 283:33175–33182

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Colbert CL, Becker N, Wei Y, Levine B (2008) Molecular basis of the regulation of Beclin 1-dependent autophagy by the γ-herpesvirus 68 Bcl-2 homolog M11. Autophagy 4:989–997

    Google Scholar 

  • Strauss JH, Strauss EG (1994) The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491–562

    CAS  PubMed  Google Scholar 

  • Sunil-Chandra NP, Arno J, Fazakerley J, Nash AA (1994) Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am J Pathol 145:818–826

    CAS  PubMed  Google Scholar 

  • Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, Liang C, Jung JU, Cheng JQ, Mul JJ, et al (2007) Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol 9:1142–1151

    Article  CAS  PubMed  Google Scholar 

  • Tallóczy Z, Jiang W, Virgin HW IV, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B (2002) Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc Natl Acad Sci USA 99:190–195

    Article  PubMed  Google Scholar 

  • Tallóczy Z, Virgin HW IV, Levine B (2006) PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2:24–29

    PubMed  Google Scholar 

  • Tarakanova VL, Suarez F, Tibbetts SA, Jacoby MA, Weck KE, Hess JL, Speck SH, Virgin HW IV (2005) Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB β2 microglobulin-deficient mice. J Virol 79:14668–14679

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30:678–688

    Article  CAS  PubMed  Google Scholar 

  • Whitley RJ, Roizman B (2001) Herpes simplex virus infections. The Lancet 357:1513–1518

    Article  CAS  Google Scholar 

  • Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109

    Article  CAS  PubMed  Google Scholar 

  • Yip KW, Reed JC (2008) Bcl-2 family proteins and cancer. Oncogene 27:6398–6406

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Strandberg L, Lenardo MJ (2008) The selectivity of autophagy and its role in cell death and survival. Autophagy 4:567–573

    PubMed  Google Scholar 

  • Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 100:15077–15082

    Article  CAS  PubMed  Google Scholar 

  • Zhou D, Spector SA (2008) Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS 22:695–699

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We apologize to authors whose work could not be included due to space restrictions. We thank Deborah Shaw for administrative support. The work in the authors’ laboratory was supported by NIH grants R01 A10151367 (B.L.) and T32 A1007520 (A.O), and an Ellison Medical Foundation Senior Scholars Award in Infectious Diseases (B.L.).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Anthony Orvedahl

  2. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Anthony Orvedahl

  3. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Beth Levine

  4. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Beth Levine

  5. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Beth Levine

Authors
  1. Anthony Orvedahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beth Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beth Levine .

Editor information

Editors and Affiliations

  1. Southwestern Medical Center, University of Texas, Harry Hines Blvd. 5323, Dallas, 75390-9113, U.S.A.

    Beth Levine

  2. Research Inst. Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan

    Tamotsu Yoshimori

  3. Health Sciences Center, University of New Mexico, Camino de Salud NE., 915, Albuquerque, 87131, U.S.A.

    Vojo Deretic

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Orvedahl, A., Levine, B. (2009). Autophagy in Mammalian Antiviral Immunity. In: Levine, B., Yoshimori, T., Deretic, V. (eds) Autophagy in Infection and Immunity. Current Topics in Microbiology and Immunology, vol 335. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00302-8_13

Download citation

Publish with us

Policies and ethics

Search

Navigation