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Archives of Virology

, Volume 161, Issue 5, pp 1285–1293 | Cite as

Interferon-inducible GTPase: a novel viral response protein involved in rabies virus infection

  • Ling Li
  • Hualei Wang
  • Hongli Jin
  • Zengguo Cao
  • Na Feng
  • Yongkun Zhao
  • Xuexing Zheng
  • Jianzhong Wang
  • Qian Li
  • Guoxing Zhao
  • Feihu Yan
  • Lina Wang
  • Tiecheng Wang
  • Yuwei Gao
  • Changchun Tu
  • Songtao Yang
  • Xianzhu Xia
Original Article

Abstract

Rabies virus infection is a major public health concern because of its wide host-interference spectrum and nearly 100 % lethality. However, the interactions between host and virus remain unclear. To decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. In this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible GTPases, and leucine-rich repeat-containing protein 16C were the three outstanding groups among these proteins. Interferon-inducible GTPases were prominent because of their strong upregulation. Moreover, quantitative real-time PCR showed distinct upregulation of interferon-inducible GTPases at the level of transcription. Several studies have shown that interferon-inducible GTPases are involved in many biological processes, such as viral infection, endoplasmic reticulum stress response, and autophagy. These findings indicate that interferon-inducible GTPases are likely to be a potential target involved in rabies pathogenesis or the antiviral process.

Keywords

Glial Fibrillary Acidic Protein Rabies Rabies Virus Infection Tetraethylammonium Bromide Challenge Virus Standard 
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

This work was supported in part by the National Natural Science Foundation of China (No. 31472175, 81171555), the National Natural Science Foundation for Young Scholars (No. 31101791), China Postdoctoral Science Foundation Grant (No. 2014T71003 and 2012M512108) and the Science and Technology Development Plan of Jilin Province (No. 20140520174JH).

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

705_2016_2795_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)
705_2016_2795_MOESM2_ESM.xlsx (505 kb)
Supplementary material 2 (XLSX 504 kb)
705_2016_2795_MOESM3_ESM.docx (19 kb)
Supplementary material 3 (DOCX 18 kb)

References

  1. 1.
    Albertini AA, Ruigrok RW, Blondel D (2011) Rabies virus transcription and replication. Adv Virus Res 79:1–22CrossRefPubMedGoogle Scholar
  2. 2.
    Anderson SL, Carton JM, Lou J, Xing L, Rubin BY (1999) Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus. Virology 256:8–14CrossRefPubMedGoogle Scholar
  3. 3.
    Bantscheff M, Lemeer S, Savitski MM, Kuster B (2012) Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present. Anal Bioanal Chem 404:939–965CrossRefPubMedGoogle Scholar
  4. 4.
    Bordignon J, Probst CM, Mosimann AL, Pavoni DP, Stella V, Buck GA, Satproedprai N, Fawcett P, Zanata SM, de Noronha L, Krieger MA, Duarte Dos Santos CN (2008) Expression profile of interferon stimulated genes in central nervous system of mice infected with dengue virus Type-1. Virology 377:319–329CrossRefPubMedGoogle Scholar
  5. 5.
    Bougneres L, Helft J, Tiwari S, Vargas P, Chang BH, Chan L, Campisi L, Lauvau G, Hugues S, Kumar P, Kamphorst AO, Dumenil AM, Nussenzweig M, MacMicking JD, Amigorena S, Guermonprez P (2009) A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells. Immunity 31:232–244CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Chang D, Zhu Y, An L, Liu J, Su L, Guo Y, Chen Z, Wang Y, Wang L, Wang J, Li T, Fang X, Fang C, Yang R, Liu C (2013) A multi-omic analysis of an Enterococcus faecium mutant reveals specific genetic mutations and dramatic changes in mRNA and protein expression. BMC Microbiol 13:304CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Colicelli J (2004) Human RAS superfamily proteins and related GTPases. Sci STKE 2004:RE13Google Scholar
  8. 8.
    Duran A, Alvarez-Mon M, Valero N (2014) Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections. Invest Clin 55:61–81PubMedGoogle Scholar
  9. 9.
    Faber M, Faber ML, Li J, Preuss MAR, Schnell MJ, Dietzschold B (2007) Dominance of a nonpathogenic glycoprotein gene over a pathogenic glycoprotein gene in rabies virus. J Virol 81:7041–7047CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gregoire 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, Andre P, Lotteau V, Biard-Piechaczyk M, Rabourdin-Combe C, Faure M (2011) IRGM is a common target of RNA viruses that subvert the autophagy network. PLoS Pathog 7:e1002422CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gregoire IP, Rabourdin-Combe C, Faure M (2012) Autophagy and RNA virus interactomes reveal IRGM as a common target. Autophagy 8:1136–1137CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Haller O, Kochs G (2011) Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity. J Interferon Cytokine Res 31:79–87CrossRefPubMedGoogle Scholar
  13. 13.
    Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, Costa P, Freuling CM, Hiby E, Knopf L, Leanes F, Meslin FX, Metlin A, Miranda ME, Muller T, Nel LH, Recuenco S, Rupprecht CE, Schumacher C, Taylor L, Vigilato MA, Zinsstag J, Dushoff J, Global Alliance for Rabies Control Partners for Rabies P (2015) Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 9:e0003709CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Han SY, Kim SH, Heasley LE (2002) Differential gene regulation by specific gain-of-function JNK1 proteins expressed in Swiss 3T3 fibroblasts. J Biol Chem 277:47167–47174CrossRefPubMedGoogle Scholar
  15. 15.
    Hu Y, Wang J, Yang B, Zheng N, Qin M, Ji Y, Lin G, Tian L, Wu X, Wu L, Sun B (2011) Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7. J Immunol 187:6456–6462CrossRefPubMedGoogle Scholar
  16. 16.
    Ito N, Moseley GW, Blondel D, Shimizu K, Rowe CL, Ito Y, Masatani T, Nakagawa K, Jans DA, Sugiyama M (2010) Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity. J Virol 84:6699–6710CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucl Acids Res 38:D355–D360CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kim BH, Shenoy AR, Kumar P, Bradfield CJ, MacMicking JD (2012) IFN-inducible GTPases in host cell defense. Cell Host Microbe 12:432–444CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li XQ, Sarmento L, Fu ZF (2005) Degeneration of neuronal processes after infection with pathogenic, but not attenuated, rabies viruses. J Virol 79:10063–10068CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Liang Y, Cucchetti M, Roncagalli R, Yokosuka T, Malzac A, Bertosio E, Imbert J, Nijman IJ, Suchanek M, Saito T, Wulfing C, Malissen B, Malissen M (2013) The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells. Nat Immunol 14:858–866CrossRefPubMedGoogle Scholar
  21. 21.
    Liu Z, Zhang HM, Yuan J, Ye X, Taylor GA, Yang D (2012) The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway. Cell Microbiol 14:133–146CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    MacMicking JD (2004) IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol 25:601–609CrossRefPubMedGoogle Scholar
  23. 23.
    MacMicking JD (2012) Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat Rev Immunol 12:367–382CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Martens S, Howard J (2006) The interferon-inducible GTPases. Ann Rev Cell Dev Biol 22:559–589CrossRefGoogle Scholar
  25. 25.
    Maxwell KL, Frappier L (2007) Viral proteomics. Microbiol Mol Biol Rev 71:398–411CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Petkova DS, Viret C, Faure M (2012) IRGM in autophagy and viral infections. Front Immunol 3:426PubMedPubMedCentralGoogle Scholar
  27. 27.
    Premzl M (2012) Comparative genomic analysis of eutherian interferon-gamma-inducible GTPases. Funct Integr Genomics 12:599–607CrossRefPubMedGoogle Scholar
  28. 28.
    Scheffzek K, Ahmadian MR (2005) GTPase activating proteins: structural and functional insights 18 years after discovery. Cell Mol Life Sci 62:3014–3038CrossRefPubMedGoogle Scholar
  29. 29.
    Scott CA, Rossiter JP, Andrew RD, Jackson AC (2008) Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome of experimental rabies in yellow fluorescent protein-expressing transgenic mice. J Virol 82:513–521CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JD (2012) GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science 336:481–485CrossRefPubMedGoogle Scholar
  31. 31.
    Taylor GA (2007) IRG proteins: key mediators of interferon-regulated host resistance to intracellular pathogens. Cell Microbiol 9:1099–1107CrossRefPubMedGoogle Scholar
  32. 32.
    Traver MK, Henry SC, Cantillana V, Oliver T, Hunn JP, Howard JC, Beer S, Pfeffer K, Coers J, Taylor GA (2011) Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. J Biol Chem 286:30471–30480CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Vaziri B, Torkashvand F, Eslami N, Fayaz A (2012) Comparative proteomics analysis of mice lymphocytes in early stages of infection by different strains of rabies virus. Indian J Virol 23:311–316CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Venugopal AK, Ghantasala SS, Selvan LD, Mahadevan A, Renuse S, Kumar P, Pawar H, Sahasrabhuddhe NA, Suja MS, Ramachandra YL, Prasad TS, Madhusudhana SN, Hc H, Chaerkady R, Satishchandra P, Pandey A, Shankar SK (2013) Quantitative proteomics for identifying biomarkers for Rabies. Clin Proteomics 10:3CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Verhelst J, Parthoens E, Schepens B, Fiers W, Saelens X (2012) Interferon-inducible protein Mx1 inhibits influenza virus by interfering with functional viral ribonucleoprotein complex assembly. J Virol 86:13445–13455CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Vidy A, Chelbi-Alix M, Blondel D (2005) Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. J Virol 79:14411–14420CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wang X, Zhang S, Sun C, Yuan ZG, Wu X, Wang D, Ding Z, Hu R (2011) Proteomic profiles of mouse neuro N2a cells infected with variant virulence of rabies viruses. J Microbiol Biotechnol 21:366–373CrossRefPubMedGoogle Scholar
  38. 38.
    Wang ZW, Sarmento L, Wang Y, Li XQ, Dhingra V, Tseggai T, Jiang B, Fu ZF (2005) Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system. J Virol 79:12554–12565CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Wiltzer L, Okada K, Yamaoka S, Larrous F, Kuusisto HV, Sugiyama M, Blondel D, Bourhy H, Jans DA, Ito N, Moseley GW (2014) Interaction of rabies virus P-protein with STAT proteins is critical to lethal rabies disease. J Infect Dis 209:1744–1753CrossRefPubMedGoogle Scholar
  40. 40.
    Yamaoka S, Ito N, Ohka S, Kaneda S, Nakamura H, Agari T, Masatani T, Nakagawa K, Okada K, Okadera K, Mitake H, Fujii T, Sugiyama M (2013) Involvement of the rabies virus phosphoprotein gene in neuroinvasiveness. J Virol 87:12327–12338CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Yang Y, Liu W, Yan G, Luo Y, Zhao J, Yang X, Mei M, Wu X, Guo X (2015) iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG. Front Microbiol 6:691PubMedPubMedCentralGoogle Scholar
  42. 42.
    Zandi F, Eslami N, Soheili M, Fayaz A, Gholami A, Vaziri B (2009) Proteomics analysis of BHK-21 cells infected with a fixed strain of rabies virus. Proteomics 9:2399–2407CrossRefPubMedGoogle Scholar
  43. 43.
    Zandi F, Eslami N, Torkashvand F, Fayaz A, Khalaj V, Vaziri B (2013) Expression changes of cytoskeletal associated proteins in proteomic profiling of neuroblastoma cells infected with different strains of rabies virus. J Med Virol 85:336–347CrossRefPubMedGoogle Scholar
  44. 44.
    Zhang J, Wu X, Zan J, Wu Y, Ye C, Ruan X, Zhou J (2013) Cellular chaperonin CCTgamma contributes to rabies virus replication during infection. J Virol 87:7608–7621CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Zhao P, Zhao L, Zhang T, Qi Y, Wang T, Liu K, Wang H, Feng H, Jin H, Qin C, Yang S, Xia X (2011) Innate immune response gene expression profiles in central nervous system of mice infected with rabies virus. Comp Immunol Microbiol Infect Dis 34:503–512CrossRefPubMedGoogle Scholar
  46. 46.
    Zhao P, Yang Y, Feng H, Zhao L, Qin J, Zhang T, Wang H, Yang S, Xia X (2013) Global gene expression changes in BV2 microglial cell line during rabies virus infection. Infect Genet Evol 20:257–269CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Ling Li
    • 1
    • 2
  • Hualei Wang
    • 2
    • 4
  • Hongli Jin
    • 2
    • 3
  • Zengguo Cao
    • 2
  • Na Feng
    • 2
    • 4
  • Yongkun Zhao
    • 2
    • 4
  • Xuexing Zheng
    • 2
    • 4
  • Jianzhong Wang
    • 2
    • 5
  • Qian Li
    • 2
  • Guoxing Zhao
    • 1
    • 2
  • Feihu Yan
    • 2
  • Lina Wang
    • 2
  • Tiecheng Wang
    • 2
  • Yuwei Gao
    • 2
    • 4
  • Changchun Tu
    • 2
  • Songtao Yang
    • 2
    • 4
  • Xianzhu Xia
    • 2
    • 4
  1. 1.College of Veterinary MedicineJilin UniversityChangchunChina
  2. 2.Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military VeterinaryAcademy of Military Medical SciencesChangchunChina
  3. 3.Changchun SR Biological Technology Co., Ltd.ChangchunChina
  4. 4.Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and ZoonosesYangzhouChina
  5. 5.Department of Animal Science and Veterinary MedicineHenan Institute of Science and TechnologyXinxiangChina

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