Advertisement

Autophagy in Mammalian Antiviral Immunity

  • Anthony Orvedahl
  • Beth LevineEmail author
Chapter
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Human Immunodeficiency Virus Autophagy Induction Sindbis Virus Viral Component Autophagy Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.).

References

  1. 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 81:12128–12134CrossRefPubMedGoogle Scholar
  2. Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS (2008) Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE 3:e2906CrossRefPubMedGoogle Scholar
  3. 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 319:921–926CrossRefPubMedGoogle Scholar
  4. 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 28:799–809CrossRefPubMedGoogle Scholar
  5. Chaumorcel M, Souquère S, Pierron G, Codogno P, Esclatine A (2008) Human cytomegalovirus controls a new autophagy-dependent cellular antiviral defense mechanism. Autophagy 4:46–53PubMedGoogle Scholar
  6. 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 250:1262–1266CrossRefPubMedGoogle Scholar
  7. 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 91:5247–5251CrossRefPubMedGoogle Scholar
  8. 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 186:1547–1557CrossRefPubMedGoogle Scholar
  9. Delgado MA, Elmaoued RA, Davis AS, Kyei G, Deretic V (2008) Toll-like receptors control autophagy. Embo J 27:1110–1121CrossRefPubMedGoogle Scholar
  10. 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 4:998–1008PubMedGoogle Scholar
  11. 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 116:2161–2172CrossRefPubMedGoogle Scholar
  12. Finlay BB, McFadden G (2006) Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124:767–782CrossRefPubMedGoogle Scholar
  13. Gandhi MK, Khanna R (2004) Human cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 4:725–738CrossRefPubMedGoogle Scholar
  14. 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 238:189–197CrossRefPubMedGoogle Scholar
  15. 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 70:84–90PubMedGoogle Scholar
  16. 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 94:843–848CrossRefGoogle Scholar
  17. He C, Orvedahl A (2007) 2007 keystone symposium on autophagy in health and disease. Autophagy 3:527–536PubMedGoogle Scholar
  18. Johnston C, Jiang W, Chu T, Levine B (2001) Identification of genes involved in the host response to neurovirulent alphavirus infection. J Virol 75:10431–10445CrossRefPubMedGoogle Scholar
  19. 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:e25CrossRefPubMedGoogle Scholar
  20. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–1401CrossRefPubMedGoogle Scholar
  21. Levine B (2002) Apoptosis in viral infections of neurons: a protective or pathologic host response? Curr Top Microbiol Immunol 265: 95–118PubMedGoogle Scholar
  22. Levine B (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120:159–162PubMedGoogle Scholar
  23. Levine B (2007) Cell biology: autophagy and cancer. Nature 446:745–747CrossRefPubMedGoogle Scholar
  24. Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7:767–777CrossRefPubMedGoogle Scholar
  25. Levine B, Goldman JE, Jiang HH, Griffin DE, Hardwick JM (1996) Bc1-2 protects mice against fatal alphavirus encephalitis. Proc Natl Acad Sci USA 93:4810–4815CrossRefPubMedGoogle Scholar
  26. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42CrossRefPubMedGoogle Scholar
  27. Levine B, Sinha S, Kroemer G (2008) Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4:600–606PubMedGoogle Scholar
  28. 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 5:832–835CrossRefPubMedGoogle Scholar
  29. 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 8:688–699CrossRefPubMedGoogle Scholar
  30. Liang XH, Goldman JE, Jiang HH, Levine B (1999) Resistance of interleukin-1β-deficient mice to fatal Sindbis virus encephalitis. J Virol 73:2563–2567PubMedGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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 121:567–577CrossRefPubMedGoogle Scholar
  33. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752CrossRefPubMedGoogle Scholar
  34. 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 71:5560–5569PubMedGoogle Scholar
  35. Mettenleiter TC, Klupp BG, Granzow H (2006) Herpesvirus assembly: a tale of two membranes. Curr Opin Microbiol 9:423–429CrossRefPubMedGoogle Scholar
  36. 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 75:5189–5196CrossRefPubMedGoogle Scholar
  37. 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 349:254–263CrossRefPubMedGoogle Scholar
  38. 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 72:452–459PubMedGoogle Scholar
  39. 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 1:23–35CrossRefPubMedGoogle Scholar
  40. Orvedahl A, Levine B (2008) Autophagy and viral neurovirulence. Cell Microbiol 10:1747–1756CrossRefPubMedGoogle Scholar
  41. Orvedahl A, Levine B (2009) Eating the enemy within: autophagy in infectious diseases. Cell Death Differ 16:57–69CrossRefPubMedGoogle Scholar
  42. 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 122:927–939CrossRefPubMedGoogle Scholar
  43. 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 112:1809–1820PubMedGoogle Scholar
  44. 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 456:264–268CrossRefPubMedGoogle Scholar
  45. Schmid D, Pypaert M, Munz C (2007) Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26:79–92CrossRefPubMedGoogle Scholar
  46. Shi CS, Kehrl JH (2008) MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J Biol Chem 283:33175–33182CrossRefPubMedGoogle Scholar
  47. 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 4:989–997Google Scholar
  48. Strauss JH, Strauss EG (1994) The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491–562PubMedGoogle Scholar
  49. Sunil-Chandra NP, Arno J, Fazakerley J, Nash AA (1994) Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am J Pathol 145:818–826PubMedGoogle Scholar
  50. 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 9:1142–1151CrossRefPubMedGoogle Scholar
  51. 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 99:190–195CrossRefPubMedGoogle Scholar
  52. Tallóczy Z, Virgin HW IV, Levine B (2006) PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2:24–29PubMedGoogle Scholar
  53. 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 79:14668–14679CrossRefPubMedGoogle Scholar
  54. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30:678–688CrossRefPubMedGoogle Scholar
  55. Whitley RJ, Roizman B (2001) Herpes simplex virus infections. The Lancet 357:1513–1518CrossRefGoogle Scholar
  56. Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109CrossRefPubMedGoogle Scholar
  57. Yip KW, Reed JC (2008) Bcl-2 family proteins and cancer. Oncogene 27:6398–6406CrossRefPubMedGoogle Scholar
  58. Yu L, Strandberg L, Lenardo MJ (2008) The selectivity of autophagy and its role in cell death and survival. Autophagy 4:567–573PubMedGoogle Scholar
  59. 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 100:15077–15082CrossRefPubMedGoogle Scholar
  60. Zhou D, Spector SA (2008) Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS 22:695–699CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of MicrobiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasUSA
  4. 4.Department of MicrobiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Howard Hughes Medical InstituteUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations