BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Systems biology of virus-host signaling network interactions

  • Received : 2012.03.01
  • Published : 2012.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Viruses have evolved to manipulate the host cell machinery for virus propagation, in part by interfering with the host cellular signaling network. Molecular studies of individual pathways have uncovered many viral host-protein targets; however, it is difficult to predict how viral perturbations will affect the signaling network as a whole. Systems biology approaches rely on multivariate, context-dependent measurements and computational analysis to elucidate how viral infection alters host cell signaling at a network level. Here we describe recent advances in systems analyses of signaling networks in both viral and non-viral biological contexts. These approaches have the potential to uncover virus- mediated changes to host signaling networks, suggest new therapeutic strategies, and assess how cell-to-cell variability affects host responses to infection. We argue that systems approaches will both improve understanding of how individual virus-host protein interactions fit into the progression of viral pathogenesis and help to identify novel therapeutic targets.

Keywords

References

  1. Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, O., Gjertsen, B. T. and Nolan, G. P. (2004) Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell 118, 217-228. https://doi.org/10.1016/j.cell.2004.06.028
  2. Miller-Jensen, K., Janes, K. A., Wong, Y. L., Griffith, L. G. and Lauffenburger, D. A. (2006) Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor necrosis-factor-induced apoptosis. J. Cell Sci. 119, 3788-3798. https://doi.org/10.1242/jcs.03102
  3. Pawson, T. and Warner, N. (2007) Oncogenic re-wiring of cellular signaling pathways. Oncogene 26, 1268-1275. https://doi.org/10.1038/sj.onc.1210255
  4. Dyer, M. D., Murali, T. M. and Sobral, B. W. (2008) The landscape of human proteins interacting with viruses and other pathogens. PLoS Pathog. 4, e32. https://doi.org/10.1371/journal.ppat.0040032
  5. Kingsmore, S. F. (2006) Multiplexed protein measurement: technologies and applications of protein and antibody arrays. Nat. Rev. Drug Discov. 5, 310-320. https://doi.org/10.1038/nrd2006
  6. Domon, B. and Aebersold, R. (2006) Mass spectrometry and protein analysis. Science 312, 212-217. https://doi.org/10.1126/science.1124619
  7. Perfetto, S. P., Chattopadhyay, P. K. and Roederer, M. (2004) Seventeen-colour flow cytometry: unravelling the immune system. Nat. Rev. Immunol. 4, 648-655. https://doi.org/10.1038/nri1416
  8. Ornatsky, O., Bandura, D., Baranov, V., Nitz, M., Winnik, M. A. and Tanner, S. (2010) Highly multiparametric analysis by mass cytometry. J. Immunol. Methods 361, 1-20. https://doi.org/10.1016/j.jim.2010.07.002
  9. Cox, M. G., van der Zwaag, P. A., van der Werf, C., van der Smagt, J. J., Noorman, M., Bhuiyan, Z. A., Wiesfeld, A. C., Volders, P. G., van Langen, I. M., Atsma, D. E., Dooijes, D., van den Wijngaard, A., Houweling, A. C., Jongbloed, J. D., Jordaens, L., Cramer, M. J., Doevendans, P. A., de Bakker, J. M., Wilde, A. A., van Tintelen, J. P. and Hauer, R. N. (2011) Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study. Circulation 123, 2690-2700. https://doi.org/10.1161/CIRCULATIONAHA.110.988287
  10. Shapira, S. D., Gat-Viks, I., Shum, B. O., Dricot, A., de Grace, M. M., Wu, L., Gupta, P. B., Hao, T., Silver, S. J., Root, D. E., Hill, D. E., Regev, A. and Hacohen, N. (2009) A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 139, 1255-1267. https://doi.org/10.1016/j.cell.2009.12.018
  11. Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., Lieberman, J. and Elledge, S. J. (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319, 921-926. https://doi.org/10.1126/science.1152725
  12. Konig, R., Zhou, Y., Elleder, D., Diamond, T. L., Bonamy, G. M., Irelan, J. T., Chiang, C. Y., Tu, B. P., De Jesus, P. D., Lilley, C. E., Seidel, S., Opaluch, A. M., Caldwell, J. S., Weitzman, M. D., Kuhen, K. L., Bandyopadhyay, S., Ideker, T., Orth, A. P., Miraglia, L. J., Bushman, F. D., Young, J. A. and Chanda, S. K. (2008) Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135, 49-60. https://doi.org/10.1016/j.cell.2008.07.032
  13. Zhou, H., Xu, M., Huang, Q., Gates, A. T., Zhang, X. D., Castle, J. C., Stec, E., Ferrer, M., Strulovici, B., Hazuda, D. J. and Espeseth, A. S. (2008) Genome-scale RNAi screen for host factors required for HIV replication. Cell Host. Microbe. 4, 495-504. https://doi.org/10.1016/j.chom.2008.10.004
  14. McDermott, J. E., Shankaran, H., Eisfeld, A. J., Belisle, S. E., Neuman, G., Li, C., McWeeney, S., Sabourin, C., Kawaoka, Y., Katze, M. G. and Waters, K. M. (2011) Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. BMC Syst. Biol. 5, 190. https://doi.org/10.1186/1752-0509-5-190
  15. Albeck, J. G., MacBeath, G., White, F. M., Sorger, P. K., Lauffenburger, D. A. and Gaudet, S. (2006) Collecting and organizing systematic sets of protein data. Nat. Rev. Mol. Cell Biol. 7, 803-812. https://doi.org/10.1038/nrm2042
  16. Janes, K. A. and Lauffenburger, D. A. (2006) A biological approach to computational models of proteomic networks. Curr. Opin. Chem. Biol. 10, 73-80. https://doi.org/10.1016/j.cbpa.2005.12.016
  17. Davey, N. E., Trave, G. and Gibson, T. J. (2011) How viruses hijack cell regulation. Trends. Biochem. Sci. 36, 159-169. https://doi.org/10.1016/j.tibs.2010.10.002
  18. Saez-Rodriguez, J., Alexopoulos, L. G., Epperlein, J., Samaga, R., Lauffenburger, D. A., Klamt, S. and Sorger, P. K. (2009) Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transduction. Mol. Syst. Biol. 5, 331.
  19. Lederer, S., Favre, D., Walters, K. A., Proll, S., Kanwar, B., Kasakow, Z., Baskin, C. R., Palermo, R., McCune, J. M. and Katze, M. G. (2009) Transcriptional profiling in pathogenic and non-pathogenic SIV infections reveals significant distinctions in kinetics and tissue compartmentalization. PLoS Pathog. 5, e1000296. https://doi.org/10.1371/journal.ppat.1000296
  20. Lawhon, S. D., Khare, S., Rossetti, C. A., Everts, R. E., Galindo, C. L., Luciano, S. A., Figueiredo, J. F., Nunes, J. E., Gull, T., Davidson, G. S., Drake, K. L., Garner, H. R., Lewin, H. A., Baumler, A. J. and Adams, L. G. (2011) Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach. PLoS One 6, e26869. https://doi.org/10.1371/journal.pone.0026869
  21. Garmaroudi, F. S., Marchant, D., Si, X., Khalili, A., Bashashati, A., Wong, B. W., Tabet, A., Ng, R. T., Murphy, K., Luo, H., Janes, K. A. and McManus, B. M. (2010) Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection. Proc. Natl. Acad. Sci. USA 107, 17053-17058. https://doi.org/10.1073/pnas.1006478107
  22. Lee, A. W., Sharp, E. R., O'Mahony, A., Rosenberg, M. G., Israelski, D. M., Nolan, G. P. and Nixon, D. F. (2008) Single-cell, phosphoepitope-specific analysis demonstrates cell type- and pathway-specific dysregulation of Jak/STAT and MAPK signaling associated with in vivo human immunodeficiency virus type 1 infection. J. Virol. 82, 3702-3712. https://doi.org/10.1128/JVI.01582-07
  23. Alexopoulos, L. G., Saez-Rodriguez, J., Cosgrove, B. D., Lauffenburger, D. A. and Sorger, P. K. (2010) Networks inferred from biochemical data reveal profound differences in toll-like receptor and inflammatory signaling between normal and transformed hepatocytes. Mol. Cell Proteomics 9, 1849-1865. https://doi.org/10.1074/mcp.M110.000406
  24. Simmons, A., Aluvihare, V. and McMichael, A. (2001) Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity 14, 763-777. https://doi.org/10.1016/S1074-7613(01)00158-3
  25. Franke, R., Muller, M., Wundrack, N., Gilles, E. D., Klamt, S., Kahne, T. and Naumann, M. (2008) Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction. BMC Syst. Biol. 2, 4. https://doi.org/10.1186/1752-0509-2-4
  26. Rogers, L. D., Brown, N. F., Fang, Y., Pelech, S. and Foster, L. J. (2011) Phosphoproteomic analysis of Salmonella-infected cells identifies key kinase regulators and SopB-dependent host phosphorylation events. Sci. Signal. 4, rs9. https://doi.org/10.1126/scisignal.2001668
  27. Janes, K. A., Albeck, J. G., Gaudet, S., Sorger, P. K., Lauffenburger, D. A. and Yaffe, M. B. (2005) A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis. Science 310, 1646-1653. https://doi.org/10.1126/science.1116598
  28. Miller-Jensen, K., Janes, K. A., Brugge, J. S. and Lauffenburger, D. A. (2007) Common effector processing mediates cell-specific responses to stimuli. Nature 448, 604-608. https://doi.org/10.1038/nature06001
  29. Fahey, B., Hickey, B., Kelleher, D., O'Dwyer, A. M. and O'Mara, S. M. (2007) The widely-used anti-viral drug interferon-alpha induces depressive- and anxiogenic-like effects in healthy rats. Behav. Brain Res. 182, 80-87. https://doi.org/10.1016/j.bbr.2007.05.005
  30. Guido, M., Bortolotti, F., Jara, P., Giacomelli, L., Fassan, M., Hierro, L., Nebbia, G., Zancan, L. and Rugge, M. (2006) Liver steatosis in children with chronic hepatitis C. Am. J. Gastroenterol. 101, 2611-2615. https://doi.org/10.1111/j.1572-0241.2006.00918.x
  31. Bortoletto, G., Scribano, L., Realdon, S., Marcolongo, M., Mirandola, S., Franceschini, L., Bonisegna, S., Noventa, F., Plebani, M., Martines, D. and Alberti, A. (2010) Hyperinsulinaemia reduces the 24-h virological response to PEG-interferon therapy in patients with chronic hepatitis C and insulin resistance. J. Viral. Hepat. 17, 475-480.
  32. Mitsos, A., Melas, I. N., Siminelakis, P., Chairakaki, A. D., Saez-Rodriguez, J. and Alexopoulos, L. G. (2009) Identifying drug effects via pathway alterations using an integer linear programming optimization formulation on phosphoproteomic data. PLoS Comput. Biol. 5, e1000591. https://doi.org/10.1371/journal.pcbi.1000591
  33. Saez-Rodriguez, J., Alexopoulos, L. G., Zhang, M., Morris, M. K., Lauffenburger, D. A. and Sorger, P. K. (2011) Comparing signaling networks between normal and transformed hepatocytes using discrete logical models. Cancer Res. 71, 5400-5411. https://doi.org/10.1158/0008-5472.CAN-10-4453
  34. Ludwig, S. (2011) Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections. Biol. Chem. 392, 837-847. https://doi.org/10.1515/bc.2011.121
  35. Kirchmair, J., Distinto, S., Liedl, K. R., Markt, P., Rollinger, J. M., Schuster, D., Spitzer, G. M. and Wolber, G. (2011) Development of anti-viral agents using molecular modeling and virtual screening techniques. Infect. Disord. Drug Targets. 11, 64-93. https://doi.org/10.2174/187152611794407782
  36. Peng, X., Chan, E. Y., Li, Y., Diamond, D. L., Korth, M. J. and Katze, M. G. (2009) Virus-host interactions: from systems biology to translational research. Curr. Opin. Microbiol. 12, 432-438. https://doi.org/10.1016/j.mib.2009.06.003
  37. Owens, C. M., Mawhinney, C., Grenier, J. M., Altmeyer, R., Lee, M. S., Borisy, A. A., Lehar, J. and Johansen, L. M. (2010) Chemical combinations elucidate pathway interactions and regulation relevant to Hepatitis C replication. Mol. Syst. Biol. 6, 375.
  38. Pirrone, V., Thakkar, N., Jacobson, J. M., Wigdahl, B. and Krebs, F. C. (2011) Combinatorial approaches to the prevention and treatment of HIV-1 infection. Antimicrob. Agents. Chemother. 55, 1831-1842. https://doi.org/10.1128/AAC.00976-10
  39. Arase, Y. (2011) Viral hepatitis: Impact of adherence to combination therapy for hepatitis C. Nat. Rev. Gastroenterol. Hepatol. 8, 248-249. https://doi.org/10.1038/nrgastro.2011.62
  40. Tsiodras, S., Mooney, J. D. and Hatzakis, A. (2007) Role of combination antiviral therapy in pandemic influenza and stockpiling implications. BMJ 334, 293-294. https://doi.org/10.1136/bmj.39105.428981.BE
  41. Chatterjee, M. S., Purvis, J. E., Brass, L. F. and Diamond, S. L. (2010) Pairwise agonist scanning predicts cellular signaling responses to combinatorial stimuli. Nat. Biotechnol. 28, 727-732. https://doi.org/10.1038/nbt.1642
  42. Bagheri, N., Shiina, M., Lauffenburger, D. A. and Korn, W. M. (2011) A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition. PLoS Comput. Biol. 7, e1001085. https://doi.org/10.1371/journal.pcbi.1001085
  43. Janes, K. A., Gaudet, S., Albeck, J. G., Nielsen, U. B., Lauffenburger, D. A. and Sorger, P. K. (2006) The response of human epithelial cells to TNF involves an inducible autocrine cascade. Cell 124, 1225-1239. https://doi.org/10.1016/j.cell.2006.01.041
  44. Herbein, G. and O'Brien, W. A. (2000) Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc. Soc. Exp. Biol. Med. 223, 241-257. https://doi.org/10.1046/j.1525-1373.2000.22335.x
  45. Niepel, M., Spencer, S. L. and Sorger, P. K. (2009) Non-genetic cell-to-cell variability and the consequences for pharmacology. Curr. Opin. Chem. Biol. 13, 556-561. https://doi.org/10.1016/j.cbpa.2009.09.015
  46. Snijder, B., Sacher, R., Ramo, P., Damm, E. M., Liberali, P. and Pelkmans, L. (2009) Population context determines cell-to-cell variability in endocytosis and virus infection. Nature 461, 520-523. https://doi.org/10.1038/nature08282
  47. Zawatzky, R., De Maeyer, E. and De Maeyer-Guignard, J. (1985) Identification of individual interferon-producing cells by in situ hybridization. Proc. Natl. Acad. Sci. U.S.A 82, 1136-1140. https://doi.org/10.1073/pnas.82.4.1136
  48. Singh, A. and Weinberger, L. S. (2009) Stochastic gene expression as a molecular switch for viral latency. Curr. Opin. Microbiol. 12, 460-466. https://doi.org/10.1016/j.mib.2009.06.016
  49. Miller-Jensen, K., Dey, S. S., Schaffer, D. V. and Arkin, A. P. (2011) Varying virulence: epigenetic control of expression noise and disease processes. Trends. Biotechnol. 29, 517-525. https://doi.org/10.1016/j.tibtech.2011.05.004
  50. Zhao, M., Zhang, J., Phatnani, H., Scheu, S. and Maniatis, T. (2012) Stochastic Expression of the Interferon-beta Gene. PLoS Biol. 10, e1001249. https://doi.org/10.1371/journal.pbio.1001249
  51. Spencer, S. L., Gaudet, S., Albeck, J. G., Burke, J. M. and Sorger, P. K. (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 459, 428-432. https://doi.org/10.1038/nature08012
  52. Weinberger, L. S., Burnett, J. C., Toettcher, J. E., Arkin, A. P. and Schaffer, D. V. (2005) Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122, 169-182. https://doi.org/10.1016/j.cell.2005.06.006
  53. Burnett, J. C., Miller-Jensen, K., Shah, P. S., Arkin, A. P. and Schaffer, D. V. (2009) Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathog. 5, e1000260. https://doi.org/10.1371/journal.ppat.1000260
  54. Chen, J. Y., Lin, J. R., Cimprich, K. A. and Meyer, T. (2012) A Two-Dimensional ERK-AKT Signaling Code for an NGF-Triggered Cell-Fate Decision. Mol. Cell. 45, 196-209. https://doi.org/10.1016/j.molcel.2011.11.023
  55. Wong, J. V., Yao, G., Nevins, J. R. and You, L. (2011) Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Mol. Cell 41, 275-285. https://doi.org/10.1016/j.molcel.2011.01.014
  56. Han, Q., Bagheri, N., Bradshaw, E. M., Hafler, D. A., Lauffenburger, D. A. and Love, J. C. (2012) Polyfunctional responses by human T cells result from sequential release of cytokines. Proc. Natl. Acad. Sci. U.S.A. 109, 1607-1612. https://doi.org/10.1073/pnas.1117194109
  57. Shin, Y. S., Remacle, F., Fan, R., Hwang, K., Wei, W., Ahmad, H., Levine, R. D. and Heath, J. R. (2011) Protein signaling networks from single cell fluctuations and information theory profiling. Biophys. J. 100, 2378-2386. https://doi.org/10.1016/j.bpj.2011.04.025
  58. Ma, C., Fan, R., Ahmad, H., Shi, Q., Comin-Anduix, B., Chodon, T., Koya, R. C., Liu, C. C., Kwong, G. A., Radu, C. G., Ribas, A. and Heath, J. R. (2011) A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells. Nat. Med. 17, 738-743. https://doi.org/10.1038/nm.2375
  59. Timm, A. and Yin, J. (2012) Kinetics of virus production from single cells. Virology 424, 11-17. https://doi.org/10.1016/j.virol.2011.12.005

Cited by

  1. A logical model of HIV-1 interactions with the T-cell activation signalling pathway vol.31, pp.7, 2015, https://doi.org/10.1093/bioinformatics/btu787
  2. Systems biology approach: Panacea for unravelling host-virus interactions and dynamics of vaccine induced immune response vol.5, 2016, https://doi.org/10.1016/j.genrep.2016.08.002
  3. Kaposi’s sarcoma: a computational approach through protein–protein interaction and gene regulatory networks analysis vol.46, pp.2, 2013, https://doi.org/10.1007/s11262-012-0865-z
  4. Virus interactions with endocytic pathways in macrophages and dendritic cells vol.21, pp.8, 2013, https://doi.org/10.1016/j.tim.2013.06.001
  5. Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth vol.88, pp.22, 2014, https://doi.org/10.1128/JVI.02538-14