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Quantitative Proteome Profiling of Street Rabies Virus-Infected Mouse Hippocampal Synaptosomes

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Abstract

It is well established now that neuronal dysfunction rather than structural damage may be responsible for the development of rabies. In order to explore the underlying mechanisms in rabies virus (RABV) and synaptic dysfunctions, a quantitative proteome profiling was carried out on synaptosome samples from mice hippocampus. Synaptosome samples from mice hippocampus were isolated and confirmed by Western blot and transmission electron microscopy. Synaptosome protein content changes were quantitatively detected by Nano-LC–MS/MS. Protein functions were classified by the Gene Ontology (GO) and KEGG pathway. PSICQUIC was used to create a network. MCODE algorithm was applied to obtain subnetworks. Of these protein changes, 45 were upregulated and 14 were downregulated following RABV infection relative to non-infected (mock) synaptosomes. 28 proteins were unique to mock treatment and 12 were unique to RABV treatment. Proteins related to metabolism and synaptic vesicle showed the most changes in expression levels. Furthermore, protein–protein interaction (PPI) networks revealed that several key biological processes related to synaptic functions potentially were modulated by RABV, including energy metabolism, cytoskeleton organization, and synaptic transmission. These data will be useful for better understanding of neuronal dysfunction of rabies and provide the foundation for future research.

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References

  1. Alandijany T, Kammouni W, Roy Chowdhury SK, Fernyhough P, Jackson AC (2013) Mitochondrial dysfunction in rabies virus infection of neurons. J Neurovirol 19(6):537–549

    Article  CAS  PubMed  Google Scholar 

  2. Bader GD, Hogue CW (2003) An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 4:2

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bai F, Witzmann FA (2007) Synaptosome proteomics. Subcell Biochem 43:77–98

    Article  PubMed  PubMed Central  Google Scholar 

  4. Baldwin ML, Rostas JA, Sim AT (2003) Two modes of exocytosis from synaptosomes are differentially regulated by protein phosphatase types 2A and 2B. J Neurochem 85(5):1190–1199

    Article  CAS  PubMed  Google Scholar 

  5. Bouzamondo E, Ladogana A, Tsiang H (1993) Alteration of potassium-evoked 5-HT release from virus-infected rat cortical synaptosomes. NeuroReport 4(5):555–558

    Article  CAS  PubMed  Google Scholar 

  6. Butterfield DA, Lange ML (2009) Multifunctional roles of enolase in Alzheimer’s disease brain: beyond altered glucose metabolism. J Neurochem 111(4):915–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cabello N, Remelli R, Canela L, Soriguera A, Mallol J, Canela EI, Robbins MJ, Lluis C, Franco R, McIlhinney RA, Ciruela F (2007) Actin-binding protein alpha-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor. J Biol Chem 282(16):12143–12153

    Article  CAS  PubMed  Google Scholar 

  8. Ceccaldi PE, Fillion MP, Ermine A, Tsiang H, Fillion G (1993) Rabies virus selectively alters 5-HT1 receptor subtypes in rat brain. Eur J Pharmacol 245(2):129–138

    Article  CAS  PubMed  Google Scholar 

  9. Deak F, Schoch S, Liu X, Sudhof TC, Kavalali ET (2004) Synaptobrevin is essential for fast synaptic-vesicle endocytosis. Nat Cell Biol 6(11):1102–1108

    Article  CAS  PubMed  Google Scholar 

  10. 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  CAS  PubMed  Google Scholar 

  11. Dumrongphol H, Srikiatkhachorn A, Hemachudha T, Kotchabhakdi N, Govitrapong P (1996) Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains. J Neurol Sci 137(1):1–6

    Article  CAS  PubMed  Google Scholar 

  12. Farahtaj F, Zandi F, Khalaj V, Biglari P, Fayaz A, Vaziri B (2013) Proteomics analysis of human brain tissue infected by street rabies virus. Mol Biol Rep 40(11):6443–6450

    Article  CAS  PubMed  Google Scholar 

  13. Griffin NM, Yu J, Long F, Oh P, Shore S, Li Y, Koziol JA, Schnitzer JE (2010) Label-free, normalized quantification of complex mass spectrometry data for proteomic analysis. Nat Biotechnol 28(1):83–89

    Article  CAS  PubMed  Google Scholar 

  14. Huang R, Gao H, Zhang L, Jia J, Liu X, Zheng P, Ma L, Li W, Deng J, Wang X, Yang L, Wang M, Xie P (2012) Borna disease virus infection perturbs energy metabolites and amino acids in cultured human oligodendroglia cells. PLoS One 7(9):e44665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Iwata M, Komori S, Unno T, Minamoto N, Ohashi H (1999) Modification of membrane currents in mouse neuroblastoma cells following infection with rabies virus. Br J Pharmacol 126(8):1691–1698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jackson AC (1993) Cholinergic system in experimental rabies in mice. Acta Virol 37(6):502–508

    CAS  PubMed  Google Scholar 

  17. Johnson JN, Ahrendt E, Braun JE (2010) CSPalpha: the neuroprotective J protein. Biochem Cell Biol 88(2):157–165

    Article  CAS  PubMed  Google Scholar 

  18. Kilbride SM, Gluchowska SA, Telford JE, O’Sullivan C, Davey GP (2011) High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal. Mol Neurodegener 6(1):53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Koprowski H (2009) Rabies in the face of the 21st century. Zoonoses Public Health 56(6–7):258–261

    Article  CAS  PubMed  Google Scholar 

  20. Ladogana A, Bouzamondo E, Pocchiari M, Tsiang H (1994) Modification of tritiated gamma-amino-n-butyric acid transport in rabies virus-infected primary cortical cultures. J Gen Virol 75(Pt 3):623–627

    Article  CAS  PubMed  Google Scholar 

  21. Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119(6):873–887

    Article  CAS  PubMed  Google Scholar 

  22. Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, Narasanna A, Kolodilov N, Dauer W, Hawkins RD, Arancio O (2004) alpha-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO J 23(22):4506–4516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mazzon M, Castro C, Roberts LD, Griffin JL, Smith GL (2014) A role for vaccinia virus protein C16 in reprogramming cellular energy metabolism. J Gen Virol 96:395–407

    Article  PubMed  Google Scholar 

  24. Millan PP (2013) Visualization and analysis of biological networks. Methods Mol Biol 1021:63–88

    Article  CAS  PubMed  Google Scholar 

  25. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13

    Article  CAS  PubMed  Google Scholar 

  26. Nakagawa T, Engler JA, Sheng M (2004) The dynamic turnover and functional roles of alpha-actinin in dendritic spines. Neuropharmacology 47(5):734–745

    Article  CAS  PubMed  Google Scholar 

  27. Orchard S (2012) Molecular interaction databases. Proteomics 12(10):1656–1662

    Article  CAS  PubMed  Google Scholar 

  28. Schutsky K, Portocarrero C, Hooper DC, Dietzschold B, Faber M (2014) Limited brain metabolism changes differentiate between the progression and clearance of rabies virus. PLoS One 9(4):e87180

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sidhu A, Wersinger C, Vernier P (2004) Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse? FASEB J 18(6):637–647

    Article  CAS  PubMed  Google Scholar 

  30. Song Y, Hou J, Qiao B, Li Y, Xu Y, Duan M, Guan Z, Zhang M, Sun L (2013) Street rabies virus causes dendritic injury and F-actin depolymerization in the hippocampus. J Gen Virol 94(Pt 2):276–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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  CAS  PubMed  Google Scholar 

  32. Varodayan FP, Harrison NL (2013) HSF1 transcriptional activity mediates alcohol induction of Vamp2 expression and GABA release. Front Integr Neurosci 7:89

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wei H, Wang W, Yarbrough JM, Baker JO, Laurens L, Van Wychen S, Chen X, Taylor LE 2nd, Xu Q, Himmel ME, Zhang M (2013) Genomic, proteomic, and biochemical analyses of oleaginous Mucor circinelloides: evaluating its capability in utilizing cellulolytic substrates for lipid production. PLoS One 8(9):e71068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wishart TM, Rooney TM, Lamont DJ, Wright AK, Morton AJ, Jackson M, Freeman MR, Gillingwater TH (2012) Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo. PLoS Genet 8(8):e1002936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zali H, Rezaei Tavirani M (2014) Meningioma protein-protein interaction network. Arch Iran Med 17(4):262–272

    CAS  PubMed  Google Scholar 

  37. 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  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by Grants from National Natural Science Foundation of China (Grant No. 31172337, 31272579, 31472208) and Natural Science Foundation of Jilin Province (Grant No. 20160101214JC).

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    Authors and Affiliations

    1. Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, 130062, Jilin, China

      Xiaoning Sun, Chunyan Dong, Maolin Zhang, Zhenhong Guan & Ming Duan

    2. Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences CAAS, Changchun, 132109, China

      Ning Shi

    3. Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun, 130012, China

      Ying Li

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    1. Xiaoning Sun
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    Correspondence to Ming Duan.

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    Xiaoning Sun, Ning Shi, and Ying Li have contributed equally to this work.

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    Sun, X., Shi, N., Li, Y. et al. Quantitative Proteome Profiling of Street Rabies Virus-Infected Mouse Hippocampal Synaptosomes. Curr Microbiol 73, 301–311 (2016). https://doi.org/10.1007/s00284-016-1061-5

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    • DOI: https://doi.org/10.1007/s00284-016-1061-5

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