Cell Stress and Chaperones

, Volume 17, Issue 6, pp 647–655 | Cite as

Loss of stress response as a consequence of viral infection: implications for disease and therapy

  • Philip L. Hooper
  • Lawrence E. Hightower
  • Paul L. Hooper
Perspective and Reflection Article

Abstract

Herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. Having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. Host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. In the case of Newcastle disease virus, the effects of viral infection on heat shock proteins may be leveraged as a therapy for cancer. Finally, the search for a specific virus being responsible for a condition like chronic fatigue syndrome may not be worthwhile if the disease is simply a nonspecific response to viral infection.

References

  1. Aridon P, Geraci F, Turturici G, D'Amelio M, Savettieri G, Sconzo G (2011) Protective role of heat shock proteins in Parkinson's disease. Neurodegener Dis 8:155–168PubMedCrossRefGoogle Scholar
  2. Beyer I, Njemini R, Bautmans I, Demanet C, Bergmann P, Mets T (2012) Inflammation-related muscle weakness and fatigue in geriatric patients. Exp Gerontol 47:52–59PubMedCrossRefGoogle Scholar
  3. Bruey J-M, Ducasse C, Bonnlaud P, Ravagnan L, Susin SA, Diaz-Latoud C, Gurbuxani S, Arrigo A-P, Kroemer G, Solary E et al (2000) Hsp27 negatively regulates cell death by interaction with cytochrome c. Nat Cell Biol 2:645–652PubMedCrossRefGoogle Scholar
  4. Burkart V, Germaschewski L, Schloot NC, Bellmann K, Kolb H (2008) Deficient heat shock protein 70 response to stress in leukocytes at onset of type 1 diabetes. Biochem Biophys Res Commun 369:421–425PubMedCrossRefGoogle Scholar
  5. Burnett H, Audas T, Liang G, Lu R (2012) Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection. Cell Stress Chaperones 17(4):473–483PubMedCrossRefGoogle Scholar
  6. Capitano ML, Ertel BR, Repasky EA, Ostberg JR (2008) Fever-range whole body hyperthermia prevents the onset of type 1 diabetes in non-obese diabetic mice. Int J Hyperthermia 24:141–149PubMedCrossRefGoogle Scholar
  7. Castle PE, Ashfaq R, Ansari F, Muller CY (2005) Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix. Cancer Lett 229:245–252PubMedCrossRefGoogle Scholar
  8. Chawla-Sarkar M, Leaman DW, Jacobs BS, Borden EC (2002) IFN-beta pretreatment sensitizes human melanoma cells to TRAIL/Apo2 ligand-induced apoptosis. J Immunol 169:847–855PubMedGoogle Scholar
  9. Chow AM, Steel R, Anderson RL (2009) Hsp72 chaperone function is dispensable for protection against stress-induced apoptosis. Cell Stress Chaperones 14:253–263PubMedCrossRefGoogle Scholar
  10. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedCrossRefGoogle Scholar
  11. Collins PL, Hightower LE (1982) Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J Virol 44:703–707PubMedGoogle Scholar
  12. Conti C, Mastromarino P, Tomao P, de Marco A, Pica F, Santoro MG (1996) Inhibition of poliovirus replication by prostaglandins A and J in human cells. Antimicrob Agents Chemother 40:367–372PubMedGoogle Scholar
  13. Conti C, de Marco A, Mastromarino P, Tomao P, Santoro MG (1999) Antiviral effect of hyperthermic treatment in rhinovirus infection. Antimicrob Agents Chemother 43:822–829PubMedGoogle Scholar
  14. D'Onofrio C, Franzese O, de Marco A, Bonmassar E, Amici C (1994) Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1 infection is independent of IL-2 and is associated with HSP70 induction. Leukemia 8:1045–1056PubMedGoogle Scholar
  15. Engin F, Hotamışlıgil GS (2010) Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic diseases. Diabetes Obes Metab 12:108–115PubMedCrossRefGoogle Scholar
  16. Foulis AK, McGill M, Farquharson MA (1991) Insulitis in type 1 (insulin-dependent) diabetes mellitus in man–macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol 165:97–103PubMedCrossRefGoogle Scholar
  17. Galluzzi L, Larochette N, Zamzami N, Kroemer G (2006) Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25:4812–4830PubMedCrossRefGoogle Scholar
  18. Glotzer JB, Saltik M, Chiocca S, Michou A-I, Moseley P, Cotten M (2000) Activation of heat-shock response by an adenovirus is essential for virus replication. Nature 407:207–211PubMedCrossRefGoogle Scholar
  19. Gutterman JU (1994) Cytokine therapeutics: lesson from interferon α. PNAS 91:1198–1205PubMedCrossRefGoogle Scholar
  20. Halder UC, Bagchi P, Chattopadhyay S, Dutta D, Chawla-Sarkar M (2011) Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway. Cell Death Dis 2:e197PubMedCrossRefGoogle Scholar
  21. Hooper PL (2007) Insulin signaling, GSK-3, heat shock proteins and the natural history of type 2 diabetes mellitus: a hypothesis. Metab Syndr Relat Disord 5:220–230PubMedCrossRefGoogle Scholar
  22. Hu S, Ciancio MJ, Lahav M, Fujiya M, Lichtenstein L, Anant S, Musch MW, Chang EB (2007) Translational inhibition of colonic epithelial heat shock proteins by IFN-gamma and TNF-alpha in intestinal inflammation. Gastroenterology 133(6):1893–1904Google Scholar
  23. Jammes Y, Steinberg J, Delliaux S, Brégeon F (2009) Chronic fatigue sydrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med 266:196–206PubMedCrossRefGoogle Scholar
  24. Jammes Y, Steinberg J, Delliaux S (2012) Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 272(1):74–84PubMedGoogle Scholar
  25. Jego G, Hazoumé A, Seigneuric R, Garrido C (2010) Targeting heat shock proteins in cancer. Cancer Lett. doi:10.1016/j.canlet.2010.10.014
  26. Kaas A, Pfleger C, Kharagjitsingh AV, Schloot NC, Hansen L, Buschard K, Koeleman BP, Roep BO, Mortensen HB, Alizadeh BZ (2012) Association between age, IL-10, IFNγ, stimulated C-peptide and disease progression in children with newly diagnosed type 1 diabetes. Diabet Med 29(6):734–741PubMedCrossRefGoogle Scholar
  27. Kallmann BA, Hüther M, Tubes M, Feldkamp J, Bertrams J, Gries FA, Lampeter EF, Kolb H (1997) Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease. Diabetes 46(2):237–243PubMedCrossRefGoogle Scholar
  28. Kitay MK, Rowe DT (1996) Protein-protein interactions between Epstein–Barr virus nuclear antigen-LP and cellular gene products: binding of 70-kilodalton heat shock proteins. Virology 220:91–99PubMedCrossRefGoogle Scholar
  29. Kon M, Kiffin R, Koga H, Chapochnick J, Macian F, Vartikovski L, Cuervo AM (2011) Chaperone-mediated autophagy is required for tumor growth. Sci Transl Med 3:109–117CrossRefGoogle Scholar
  30. Kramer LD, Li J, Shi P-Y (2007) West Nile virus. Lancet Neurol 6:171–181PubMedCrossRefGoogle Scholar
  31. Kumar M, Rawat P, Khan SZ, Dhamija N, Chaudhary P, Ravi DS, Mitra D (2011) Reciprocal regulation of human immunodeficiency virus-1 gene expression and replication by heat shock proteins 40 and 70. J Mol Biol 410:944–958PubMedCrossRefGoogle Scholar
  32. Li Z, Jiang Y, Jiao P, Wang A, Zhao F, Tian G, Wang X, Yu K, Bu Z, Chen H (2006) The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 80:11115–11123PubMedCrossRefGoogle Scholar
  33. Li G, Zhang J, Tong X, Liu W, Ye X (2011) Heat shock protein 70 inhibits the activity of influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS One 6:e16546PubMedCrossRefGoogle Scholar
  34. Liao WJ, Fan PS, Fu M, Fan XL, Liu YF (2005) Increased expression of 70 kD heat shock protein in cultured primary human keratinocytes induced by human papillomavirus 16 E6/E7 gene. Chin Med J(Engl Ed) 118:2058–2062Google Scholar
  35. Lutsenko MT, Dorofienko NN, Andievskaya IA (2010) Morphofunctional characteristics of syncytiotrophoblast and content of heat shock protein 70 in it during exacerbation of herpesvirus infection in pregnant women. Bull Exp Biol Med 150:149–152PubMedCrossRefGoogle Scholar
  36. Madara J, Krewet JA, Shah M (2005) Heat shock protein 72 expression allows permissive replication of oncolytic adenovirus dl1520 (ONYX-015) in rat glioblastoma cells. Mol Cancer 4(1):12PubMedCrossRefGoogle Scholar
  37. Mammen JS, Ghazarian SR, Pulkstenis E, Subramanian GM, Rosen A, Ladenson PW (2012) Phenotypes of interferon-α-induced thyroid dysfunction among patients treated for hepatitis C are associated with pretreatment serum TSH and female sex. J Clin Endocrinol Metab. doi:10.1210/jc.2012-1026
  38. Mandansky CH, Bratt MA (1978) Noncytopathic mutants of Newcastle disease virus. J Virol 26:724–729Google Scholar
  39. Mandansky CH, Bratt MA (1981a) Noncytopathic mutants of Newcastle disease virus are defective in virus-specific RNA synthesis. J Virol 37:317–327Google Scholar
  40. Mandansky CH, Bratt MA (1981b) Relationships among virus spread, cytopathogenicity, and virulence as revealed by the noncytopathic mutants of Newcastle disease virus. J Virol 40:691–702Google Scholar
  41. Mansour M, Palese P, Zamarin D (2011) Oncolytic specificity of Newcastle disease virus is mediated by selectivity for apoptosis-resistant cells. J Virol 85:6015–6023PubMedCrossRefGoogle Scholar
  42. Mastromarino P, Conti C, Petruzziello R, de Marco A, Pica F, Santoro MG (1993) Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell-mediated event associated with heat-shock protein synthesis. Antiviral Res 20:209–222PubMedCrossRefGoogle Scholar
  43. McPherson S, Powell EE, Barrie HD, Clouston AD, McGuckin M, Jonsson JR (2011) No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol 26:319–327PubMedCrossRefGoogle Scholar
  44. Myhill S, Booth NE, McLaren-Howard J (2009) Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med 2(1):1–16PubMedGoogle Scholar
  45. Nagarja GM, Kaur P, Neumann W, Asea EE, Bausero MA, Multhoff G, Asea A (2012) Silencing hsp25/hsp27 gene expression augments proteasome activity and increases CD8+ T cell-mediated tumor killing and memory responses. Cancer Prev Res 5:122–137CrossRefGoogle Scholar
  46. Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun C, Hotamışlıgil GS (2010) Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140:338–348PubMedCrossRefGoogle Scholar
  47. Oh W, Song J (2006) Hsp70 functions as a negative regulator of West Nile virus capsid protein through direct interaction. Biochem Biophys Res Commun 347:994–1000PubMedCrossRefGoogle Scholar
  48. O'Sullivan-Murphy B, Urano F (2012) ER stress as a trigger for β-cell dysfunction and autoimmunity in type 1 diabetes. Diabetes 61:780–781PubMedCrossRefGoogle Scholar
  49. Panossian A, Wikman G, Kaur P, Asea A (2009) Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine 16:617–622PubMedCrossRefGoogle Scholar
  50. Pavlovic J, Haller O, Staeheli P (1992) Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol 66:2564–2569PubMedGoogle Scholar
  51. Radhakrishnan S, Upadhyay A, Mohan N, Dhar A, Walia HK, Zubaidi G (2005) Late development of diabetes mellitus after interferon-alfa and ribavirin therapy for chronic hepatitis C: a case report. Med Princ Pract 14:281–283PubMedCrossRefGoogle Scholar
  52. Ravindra PV, Tiwari AK, Sharma B, Chauhan RS (2009) Newcastle disease virus as an oncolytic agent. Indian J Med Res 130:507–513PubMedGoogle Scholar
  53. Reed JC (2011) Priming cancer cells for death. Science 334:1075–1076PubMedCrossRefGoogle Scholar
  54. Reyes-Del Valle J, Chávez-Salinas S, Medina F, Del Angel RM (2005) Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells. J Virol 79:4557–4567PubMedCrossRefGoogle Scholar
  55. Rossi A, Elia G, Santoro MG (1996) 2-Cyclopenten-1-one, a new inducer of heat shock protein 70 with antiviral activity. J Biol Chem 271:32192–32196PubMedCrossRefGoogle Scholar
  56. Scavone G, Zaccardi F, Manto A, Caputo S, Pitocco D, Ghirlanda G (2010) A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy. Diabetes Res Clin Pract 89:e36–e38PubMedCrossRefGoogle Scholar
  57. Shimizu K, Iguchi A, Gomyou R, Ono Y (1999) Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site. Virology 254:213–219PubMedCrossRefGoogle Scholar
  58. Silva AM, Wang D, Komar AA, Castilho BA, Williams BR (2007) Salicylates trigger protein synthesis inhibition in a protein kinase R-like endoplasmic reticulum kinase-dependent manner. J Biol Chem 282:10164–10171PubMedCrossRefGoogle Scholar
  59. Singleton KD, Wischmeyer PE (2007) Glutamine's protection against sepsis and lung injury is dependent on heat shock protein 70 expression. Am J Physiol Regul Integr Comp Physiol 292:R1839–R1845PubMedCrossRefGoogle Scholar
  60. Song H, Moseley PL, Lowe SL, Ozbun MA (2010) Inducible heat shock protein 70 enhances HPV31 viral genome replication and virion production during the differentiation-dependent life cycle in human keratinocytes. Virus Res 147:113–122PubMedCrossRefGoogle Scholar
  61. Stankiewicz AR, Lachapelle G, Foo CPZ, Radicioni SM, Mosser DD (2005) Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem 280:38729–38739PubMedCrossRefGoogle Scholar
  62. Tersey S, Nishiki Y, Templin A, Cabrera S, Stull N, Colvin S, Evans-Molina C, Rickus J, Maier B, Mirmira R (2012) Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model. Diabetes 61:818–827PubMedCrossRefGoogle Scholar
  63. Toovey S, Jick SS, Meier CR (2011) Parkinson's disease or Parkinson symptoms following seasonal influenza. Influenza Other Respi Viruses 5:328–333PubMedCrossRefGoogle Scholar
  64. Tosone G, Borgia G, Gentile I, Cerini R, Conte MC, Orlando R, Piazza M (2007) A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided? Acta Diabetol 44:167–169PubMedCrossRefGoogle Scholar
  65. Tsai MS, Chen JH, Fang YW, Yang AH, Chang CH (2012) Membranous nephropathy induced by pegylated interferon alpha-2a therapy for chronic viral hepatitis B. Clin Nephrol 77:496–500PubMedGoogle Scholar
  66. Unoshima M, Iwasaka H, Eto J, Takita-Sonoda Y, Noguchi T, Nishizono A (2003) Antiviral effects of geranylgeranylacetone: enhancement of MxA expression and phosphorylation of PKR during influenza virus infection. Antimicrob Agents Chemother 47:2914–2921PubMedCrossRefGoogle Scholar
  67. Van Coster RN, De Vivo DC, Blake D, Lombes A, Barrett R, DiMauro S (1991) Adult Reye's syndrome: a review with new evidence for a generalized defect in intramitochondrial enzyme processing. Neurology 41:1815–1821PubMedCrossRefGoogle Scholar
  68. Van Der Kelen K, Beyaert R, Inzé D, De Veylder L (2009) Translational control of eukaryotic gene expression. Crit Rev Biochem Mol Biol 44:143–168CrossRefGoogle Scholar
  69. van Eden W, van der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5:318–330PubMedCrossRefGoogle Scholar
  70. Vojdani A, Ghoneum M, Choppa PC, Magtoto L, Lapp CW (2007) Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein kinase RNA. J Intern Med 242:465–478CrossRefGoogle Scholar
  71. Wang H, Ding Y, Zhou J, Sun X, Wang S (2009) The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3. Phytomedicine 16:146–155PubMedCrossRefGoogle Scholar
  72. Weiss YG, Bouwman A, Gehan B, Schears G, Raj N, Deutschman CS (2000) Cecal ligation and double puncture impairs heat shock protein 70 (HSP-70) expression in the lungs of rats. Shock 13:19–23PubMedCrossRefGoogle Scholar
  73. Wieten L, van der Zee R, Goedemans R, Sijtsma J, Serafini M, Lubsen NH, van Eden W, Broere F (2010) Hsp expression and induction as a readout for detection of immune modulatory components in food. Cell Stress Chaperones 15:25–37PubMedCrossRefGoogle Scholar
  74. Zamarin D, Palese P (2012) Oncolyitc Newcastle disease virus for cancer therapy: old challenges and new directions. Future Microbiol 7:347–367PubMedCrossRefGoogle Scholar
  75. Zhang Q, Zhou X-D, Denny T, Ottenweller JE, Lange G, LaManca JJ, Lavietes MH, Pollet C, Gause WC, Natelson BH (1999) Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome. Clin Vaccine Immunol 6:6–13Google Scholar
  76. Zhang C, Yang Y, Zhou X, Yang Z, Liu X, Cao Z, Song H, He Y, Huange P (2011) The NS1 protein of influenza a virus interacts with Hsp90 in human alveolar basal epithelial cells: implication for virus-induced apoptosis. Virol J 8:181PubMedCrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2012

Authors and Affiliations

  • Philip L. Hooper
    • 1
  • Lawrence E. Hightower
    • 2
  • Paul L. Hooper
    • 3
    • 4
  1. 1.Division of Endocrinology, Metabolism, and Diabetes, School of MedicineUniversity of ColoradoAuroraUSA
  2. 2.Department of Molecular and Cell BiologyUniversity of ConnecticutStorrsUSA
  3. 3.Department of AnthropologyUniversity of New MexicoAlbuquerqueUSA
  4. 4.Santa Fe InstituteSanta FeUSA

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