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Proteomics analysis of human brain tissue infected by street rabies virus

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Abstract

In order to extend the knowledge of rabies pathogenesis, a two-dimensional electrophoresis/mass spectrometry based postmortem comparative proteomics analysis was carried out on human brain samples. Alteration in expression profile of several proteins was detected. Proteins related to cytoskeleton, metabolism, proteasome and immune regulatory systems showed the most changes in expression levels. Among these groups, the cytoskeleton related proteins (dynein light chain, β-centractin, tubulin alpha-1C chain and destrin) and metabolism associated proteins (fatty acid-binding protein, macrophage migration inhibitory factor, glutamine synthetase and alpha enolase) were the main altered proteins. These alterations may be considered as an evidence of disturbances in neuronal key processes including axonal transport, synaptic activity, signaling and metabolic pathways in rabies virus infected human brain.

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References

  1. Jackson AC (1991) Biological basis of rabies virus neurovirulence in mice: comparative pathogenesis study using the immunoperoxidase technique. J Virol 65(1):537–540

    PubMed  CAS  Google Scholar 

  2. Wunner WH, Briggs DJ (2010) Rabies in the 21 century. PLoS Negl Trop Dis 4(3):e591

    Article  PubMed  Google Scholar 

  3. Leung AK, Davies HD, Hon KL (2007) Rabies: epidemiology, pathogenesis, and prophylaxis. Adv Ther 24(6):1340–1347

    Article  PubMed  Google Scholar 

  4. Durai R, Venkatraman R (2006) Human rabies and its prevention. Br J Hosp Med (Lond) 67(11):588–593

    Google Scholar 

  5. Dhingra V, Li X, Liu Y, Fu ZF (2007) Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system. J Neurovirol 13(2):107–117

    Article  PubMed  CAS  Google Scholar 

  6. 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(9):2399–2407

    Article  PubMed  CAS  Google Scholar 

  7. 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(4):366–373

    PubMed  CAS  Google Scholar 

  8. Thanomsridetchai N, Singhto N, Tepsumethanon V, Shuangshoti S, Wacharapluesadee S, Sinchaikul S, Chen ST, Hemachudha T, Thongboonkerd V (2011) Comprehensive proteome analysis of hippocampus, brainstem, and spinal cord from paralytic and furious dogs naturally infected with rabies. J Proteome Res 10(11):4911–4924

    Article  PubMed  CAS  Google Scholar 

  9. 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(2):336–347

    Article  PubMed  CAS  Google Scholar 

  10. Martins-de-Souza D, Menezes de Oliveira B, dos Santos Farias A, Horiuchi RS, Crepaldi Domingues C, de Paula E, Marangoni S, Gattaz WF, Dias-Neto E, Camillo Novello J (2007) The use of ASB-14 in combination with CHAPS is the best for solubilization of human brain proteins for two-dimensional gel electrophoresis. Brief Funct Genomics Proteomics 6(1):70–75

    Article  CAS  Google Scholar 

  11. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  12. Candiano G, Bruschi M, Musante L, Santucci L, Ghiggeri GM, Carnemolla B, Orecchia P, Zardi L, Righetti PG (2004) Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis 25(9):1327–1333

    Article  PubMed  CAS  Google Scholar 

  13. Maxwell KL, Frappier L (2007) Viral proteomics. Microbiol Mol Biol Rev 71(2):398–411

    Article  PubMed  CAS  Google Scholar 

  14. Levy JR, Holzbaur EL (2006) Cytoplasmic dynein/dynactin function and dysfunction in motor neurons. Int J Dev Neurosci 24(2–3):103–111

    Article  PubMed  CAS  Google Scholar 

  15. Gulesserian T, Kim SH, Fountoulakis M, Lubec G (2002) Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain. Biochem Biophys Res Commun 291(1):62–67

    Article  PubMed  CAS  Google Scholar 

  16. Vallee RB, Williams JC, Varma D, Barnhart LE (2004) Dynein: an ancient motor protein involved in multiple modes of transport. J Neurobiol 58(2):189–200

    Article  PubMed  CAS  Google Scholar 

  17. Weng YQ, Qiu SJ, Liu YK, Fan J, Gao Q, Tang ZY (2008) Down-regulation of beta-centractin might be involved in dendritic cells dysfunction and subsequent hepatocellular carcinoma immune escape: a proteomic study. J Cancer Res Clin Oncol 134(2):179–186

    Article  PubMed  CAS  Google Scholar 

  18. Raux H, Flamand A, Blondel D (2000) Interaction of the rabies virus P protein with the LC8 dynein light chain. J Virol 74(21):10212–10216

    Article  PubMed  CAS  Google Scholar 

  19. Sarmiere PD, Bamburg JR (2004) Regulation of the neuronal actin cytoskeleton by ADF/cofilin. J Neurobiol 58(1):103–117

    Article  PubMed  CAS  Google Scholar 

  20. Ceccaldi PE, Valtorta F, Braud S, Hellio R, Tsiang H (1997) Alteration of the actin-based cytoskeleton by rabies virus. J General Virol 78(Pt 11):2831–2835

    CAS  Google Scholar 

  21. Vartiainen MK, Mustonen T, Mattila PK, Ojala PJ, Thesleff I, Partanen J, Lappalainen P (2002) The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics. Mol Biol Cell 13(1):183–194

    Article  PubMed  CAS  Google Scholar 

  22. Yeoh S, Pope B, Mannherz HG, Weeds A (2002) Determining the differences in actin binding by human ADF and cofilin. J Mol Biol 315(4):911–925

    Article  PubMed  CAS  Google Scholar 

  23. Verdoni AM, Aoyama N, Ikeda A, Ikeda S (2008) Effect of destrin mutations on the gene expression profile in vivo. Physiol Genomics 34(1):9–21

    Article  PubMed  CAS  Google Scholar 

  24. Kiuchi T, Nagai T, Ohashi K, Mizuno K (2011) Measurements of spatiotemporal changes in G-actin concentration reveal its effect on stimulus-induced actin assembly and lamellipodium extension. J Cell Biol 193(2):365–380

    Article  PubMed  CAS  Google Scholar 

  25. Wang WH, Abeydeera LR, Prather RS, Day BN (2000) Polymerization of nonfilamentous actin into microfilaments is an important process for porcine oocyte maturation and early embryo development. Biol Reprod 62(5):1177–1183

    Article  PubMed  CAS  Google Scholar 

  26. Owada Y, Yoshimoto T, Kondo H (1996) Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J Chem Neuroanat 12(2):113–122

    Article  PubMed  CAS  Google Scholar 

  27. Bacher M, Meinhardt A, Lan HY, Dhabhar FS, Mu W, Metz CN, Chesney JA, Gemsa D, Donnelly T, Atkins RC, Bucala R (1998) MIF expression in the rat brain: implications for neuronal function. Mol Med 4(4):217–230

    PubMed  CAS  Google Scholar 

  28. Murphy EJ, Owada Y, Kitanaka N, Kondo H, Glatz JF (2005) Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice. Biochemistry 44(16):6350–6360

    Article  PubMed  CAS  Google Scholar 

  29. Shioda N, Yamamoto Y, Watanabe M, Binas B, Owada Y, Fukunaga K (2010) Heart-type fatty acid binding protein regulates dopamine D2 receptor function in mouse brain. J Neurosci 30(8):3146–3155

    Article  PubMed  CAS  Google Scholar 

  30. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, Bucala R (2002) Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci USA 99(1):345–350

    Article  PubMed  CAS  Google Scholar 

  31. Bozza M, Satoskar AR, Lin G, Lu B, Humbles AA, Gerard C, David JR (1999) Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 189(2):341–346

    Article  PubMed  CAS  Google Scholar 

  32. Bernhagen J, Mitchell RA, Calandra T, Voelter W, Cerami A, Bucala R (1994) Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF). Biochemistry 33(47):14144–14155

    Article  PubMed  CAS  Google Scholar 

  33. Poon HF, Vaishnav RA, Getchell TV, Getchell ML, Butterfield DA (2006) Quantitative proteomics analysis of differential protein expression and oxidative modification of specific proteins in the brains of old mice. Neurobiol Aging 27(7):1010–1019

    Article  PubMed  CAS  Google Scholar 

  34. Robinson SR (2001) Changes in the cellular distribution of glutamine synthetase in Alzheimer’s disease. J Neurosci Res 66(5):972–980

    Article  PubMed  CAS  Google Scholar 

  35. Darman J, Backovic S, Dike S, Maragakis NJ, Krishnan C, Rothstein JD, Irani DN, Kerr DA (2004) Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. J Neurosci 24(34):7566–7575

    Article  PubMed  CAS  Google Scholar 

  36. Weli SC, Scott CA, Ward CA, Jackson AC (2006) Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity. J Virol 80(20):10270–10273

    Article  PubMed  CAS  Google Scholar 

  37. de Vrij FM, Fischer DF, van Leeuwen FW, Hol EM (2004) Protein quality control in Alzheimer’s disease by the ubiquitin proteasome system. Prog Neurobiol 74(5):249–270

    Article  PubMed  Google Scholar 

  38. Pak DT, Sheng M (2003) Targeted protein degradation and synapse remodeling by an inducible protein kinase. Science 302(5649):1368–1373

    Article  PubMed  CAS  Google Scholar 

  39. McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW (2003) Altered proteasomal function in sporadic Parkinson’s disease. Exp Neurol 179(1):38–46

    Article  PubMed  CAS  Google Scholar 

  40. McNaught KS, Jackson T, JnoBaptiste R, Kapustin A, Olanow CW (2006) Proteasomal dysfunction in sporadic Parkinson’s disease. Neurology 66(10 Suppl 4):S37–S49

    Article  PubMed  CAS  Google Scholar 

  41. McNaught KS, Olanow CW (2006) Protein aggregation in the pathogenesis of familial and sporadic Parkinson’s disease. Neurobiol Aging 27(4):530–545

    Article  PubMed  CAS  Google Scholar 

  42. Sherman MY, Goldberg AL (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29(1):15–32

    Article  PubMed  CAS  Google Scholar 

  43. Cassarino DS, Bennett JP Jr (1999) An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res 29(1):1–25

    Article  CAS  Google Scholar 

  44. Shamoto-Nagai M, Maruyama W, Kato Y, Isobe K, Tanaka M, Naoi M, Osawa T (2003) An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y cells. J Neurosci Res 74(4):589–597

    Article  PubMed  CAS  Google Scholar 

  45. Altar CA, Jurata LW, Charles V, Lemire A, Liu P, Bukhman Y, Young TA, Bullard J, Yokoe H, Webster MJ, Knable MB, Brockman JA (2005) Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry 58(2):85–96

    Article  PubMed  CAS  Google Scholar 

  46. Tholey G, Ledig M, Mandel P (1982) Modifications in energy metabolism during the development of chick glial cells and neurons in culture. Neurochem Res 7(1):27–36

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grant No. 438 from Pasteur Institute of Iran. Authors acknowledge gratefully Dr. Adam Dowle (Proteomics Technology Facility, Department of Biology, University of York, England) for his critical review on matrix-assisted laser desorption/ionization-time of flight/time of flight mass spectrometry analysis. We also thank, Fatemeh Torkashvand, Elmira Haghighatjoo, Atefeh Mirzakhani and Ahmad Adeli for technical and supportive help.

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Authors and Affiliations

  1. WHO Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran, Tehran, Iran

    Firouzeh Farahtaj, Peyvand Biglari & Ahmad Fayaz

  2. Protein Chemistry Unit, Biotechnology Research Center, Pasteur Institute of Iran, 69, Pasteur St, 13164, Tehran, Iran

    Fatemeh Zandi & Behrouz Vaziri

  3. Fungal Biotechnology Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Vahid Khalaj

Authors
  1. Firouzeh Farahtaj
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  2. Fatemeh Zandi
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  5. Ahmad Fayaz
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  6. Behrouz Vaziri
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Correspondence to Behrouz Vaziri.

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Firouzeh Farahtaj and Fatemeh Zandi have equally contributed to this work.

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Farahtaj, F., Zandi, F., Khalaj, V. et al. Proteomics analysis of human brain tissue infected by street rabies virus. Mol Biol Rep 40, 6443–6450 (2013). https://doi.org/10.1007/s11033-013-2759-0

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  • DOI: https://doi.org/10.1007/s11033-013-2759-0

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