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Deciphering the host-pathogen protein interface in chikungunya virus-mediated sickness

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Abstract

Successful infection with chikungunya virus (CHIKV) depends largely on the ability of this virus to manipulate cellular processes in its favour through specific interactions with several host factors. The knowledge of virus-host interactions is of particular value for understanding the interface through which therapeutic strategies could be applied. In the current study, the authors have employed a computational method to study the protein interactions between CHIKV and both its human host and its mosquito vector. In this structure-based study, 2028 human and 86 mosquito proteins were predicted to interact with those of CHIKV through 3918 and 112 unique interactions, respectively. This approach could predict 40 % of the experimentally confirmed CHIKV-host interactions along with several novel interactions, suggesting the involvement of CHIKV in intracellular cell signaling, programmed cell death, and transcriptional and translational regulation. The data corresponded to those obtained in earlier studies for HIV and dengue viruses using the same methodology. This study provides a conservative set of potential interactions that can be employed for future experimental studies with a view to understanding CHIKV biology.

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References

  1. Higgs S (2006) The 2005–2006 chikungunya epidemic in the Indian Ocean. Vector Borne Zoonotic Dis 6:115–116

    PubMed  Google Scholar 

  2. Rezza G, Nicoletti L, Angelini R et al (2007) Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370(9602):1840–1846

    PubMed  CAS  Google Scholar 

  3. Wang E, Volkova E, Adams AP et al (2008) Chimeric alphavirus vaccine candidates for chikungunya. Vaccine 26:5030–5039

    PubMed  CAS  Google Scholar 

  4. Tsetsarkin K, Higgs S, McGee C et al (2006) Infectious clones of chikungunya virus (La Reunion isolate) for vector competence studies. Vector Borne Zoonotic Dis 6:325–337

    Google Scholar 

  5. Arpino C, Curatolo P, Rezza G (2009) Chikungunya and the nervous system: what we do and do not know. Rev Med Virol 19:121–129

    PubMed  Google Scholar 

  6. Chandak R, Kashyap S, Kabra D, Karandikar P, Saha SS, Morey SH, Purohit J, Girdhar I, Taori M, Daginawala HF (2009) Neurological complications of chikungunya virus infection. Neurol India 57(2):177–180

    PubMed  Google Scholar 

  7. Hardy JL, Houk EJ, Kramer LD, Reeves WC (1983) Intrinsic factors affecting vector competence of mosquitoes for arboviruses. Annu Rev Entomol 28:229–262

    PubMed  CAS  Google Scholar 

  8. Aloy P, Russell RB (2003) InterPreTS: protein interaction prediction through tertiary structure. Bioinformatics 19:161

    PubMed  CAS  Google Scholar 

  9. Lu L, Lu H, Skolnick J (2002) MULTIPROSPECTOR: an algorithm for the prediction of protein-protein interactions by multimeric threading. Proteins 49:350–364

    PubMed  CAS  Google Scholar 

  10. Davis FP, Braberg H, Shen MY et al (2006) Protein complex compositions predicted by structural similarity. Nucleic Acids Res 34:2943–2952

    PubMed  CAS  Google Scholar 

  11. Dyer MD, Murali TM, Sobral BW (2007) Computational prediction of hostpathogen protein protein interactions. Bioinformatics 23:I159–I166

    PubMed  CAS  Google Scholar 

  12. Lee SA, Chan C, Tsai CH et al (2008) Ortholog-based protein-protein interaction prediction and its application to inter-species interactions. BMC Bioinformatics 9:S11

    PubMed  Google Scholar 

  13. Tastan O, Qi Y, Carbonell JG, Klein-Seetharaman J (2009) Prediction of interactions between HIV-1 and human proteins by information integration. Pac Symp Biocomput 14:516–527

    Google Scholar 

  14. Evans P, Dampier W, Ungar L, Tozeren A (2009) Prediction of HIV-1 virus host protein interactions using virus and host sequence motifs. BMC Med Genomics 2:27

    PubMed  Google Scholar 

  15. Doolittle JM, Gomez SM (2010) Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens. Virol J 7:82

    Google Scholar 

  16. Davis FP, Barkan DT, Eswar N, McKerrow JH, Sali A (2007) Host pathogen protein interactions predicted by comparative modeling. Protein Sci 16:2585

    PubMed  CAS  Google Scholar 

  17. Franzosa EA, Xia Y (2011) Structural principles within the human-virus protein-protein interaction network. PNAS 108(26):10538–10543

    PubMed  CAS  Google Scholar 

  18. Zhang QC, Petrey D, Deng L et al (2012) Structure based prediction of protein-protein interactions on a genome wide scale. Nature 490:556–561

    PubMed  CAS  Google Scholar 

  19. Davey NE, Trave G, Gibson TJ (2011) How viruses hijack cell regulation. Trends Biochem Sci 36(3):159–169

    PubMed  CAS  Google Scholar 

  20. Doolittle JM, Gomez SM (2011) Mapping protein interactions between dengue virus and its human and insect hosts. PLoS Neg Trop Dis 5(2):e954

    CAS  Google Scholar 

  21. Sreejith R, Rana J, Dudha N, Kumar K, Gabrani R, Sharma SK, Gupta A, Vrati S, Chaudhary VK, Gupta S (2012) Mapping of interactions among chikungunya virus nonstructural proteins. Virus Res 169(1):231–236

    PubMed  CAS  Google Scholar 

  22. Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28:235–242

    PubMed  CAS  Google Scholar 

  23. Yang Z (2008) I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9

  24. Dudha N, Appaiahgari MB, Bharati K, Gupta D, Gupta Y, Kumar K, Gabrani R, Sharma SK, Gupta A, Chaudhary VK, Vrati S, Gupta S (2012) Molecular cloning and characterization of chikungunya virus genes from Indian isolate of 2006 outbreak. J Pharm Res 5(7):3860–3863

    Google Scholar 

  25. Holm L, Sander C (1993) Protein structure comparison by alignment of distance matrices. J Mol Biol 233:123–138

    Google Scholar 

  26. Holm L, Kaariainen S, Rosenstrom P, Schenkel A (2008) Searching protein structure databases with DaliLite v. 3. Bioinformatics 24:2780

    PubMed  CAS  Google Scholar 

  27. Mishra GR, Suresh M, Kumaran K et al (2006) Human protein reference database—2006 update. Nucleic Acids Res 34:D411–D414

    PubMed  CAS  Google Scholar 

  28. Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M (2006) BioGRID: a general repository for interaction datasets. Nucleic Acids Res 1(34):535–539

    Google Scholar 

  29. Aranda B, Achuthan P, Alam-Faruque Y, Armean I, Bridge A et al (2009) The IntAct molecular interaction database in 2010. Nucleic Acids Res 38:D525–D531

    PubMed  Google Scholar 

  30. Berglund AC, Sjolund E, Ostlund G, Sonnhammer ELL (2007) InParanoid 6: eukaryotic ortholog clusters with inparalogs. Nucleic Acids Res 33:D76–D480

    Google Scholar 

  31. Crosby MA, Goodman JL, Strelets VB et al (2006) FlyBase: genomes by the dozen. Nucleic Acids Res 00:D1–D6

    Google Scholar 

  32. Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504

    PubMed  CAS  Google Scholar 

  33. Yu J, Pacifico S, Liu G, Finley R (2008) DroID: the Drosophila interactions database, a comprehensive resource for annotated gene and protein interactions. BMC Genomics 9:461

    PubMed  Google Scholar 

  34. Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25:25–29

    PubMed  CAS  Google Scholar 

  35. Dennis G, Sherman B, Hosack D et al (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:R60

    Google Scholar 

  36. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    CAS  Google Scholar 

  37. McCarthy F, Wang N, Magee GB et al (2006) AgBase: a functional genomics resource for agriculture. BMC Genomics 7:229

    PubMed  Google Scholar 

  38. Atasheva S, Gorchakov R, English R, Frolov I, Frolova E (2007) Development of Sindbis viruses encoding nsP2/GFP chimeric proteins and their application for studying nsP2 functioning. J Virol 81:5046–5057

    PubMed  CAS  Google Scholar 

  39. Burnham AJ, Gong L, Hardy RW (2007) Heterogeneous nuclear ribonuclear protein K interacts with Sindbis virus nonstructural proteins and viral subgenomic mRNA. Virology 367:212–221

    PubMed  CAS  Google Scholar 

  40. Cristea IM, Rozjabek H, Molloy KR et al (2010) Host factors associated with the Sindbis virus RNA-dependent RNA polymerase: role for G3BP1 and G3BP2 in virus replication. J Virol 84:6720–6732

    PubMed  CAS  Google Scholar 

  41. Frolova E, Gorchakov R, Garmashova N, Atasheva S, Vergara LA, Frolov I (2006) Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol 80:4122–4134

    PubMed  CAS  Google Scholar 

  42. Gorchakov R, Garmashova N, Frolova E, Frolov I (2008) Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 82:10088–10101

    PubMed  CAS  Google Scholar 

  43. Montgomery SA, Berglund P, Beard CW, Johnston RE (2006) Ribosomal protein S6 associates with alphavirus nonstructural protein 2 and mediates expression from alphavirus messages. J Virol 80:7729–7739

    PubMed  CAS  Google Scholar 

  44. Tchankouo-Nguetcheu S, Khun H, Pincet L, Roux P, Bahut M, Huerre M, Guette C, Choume V (2010) Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses. PLoS One 5(10):e13149

    PubMed  Google Scholar 

  45. Zhang X, Fugere M, Day R, Kielian M (2003) Furin processing and proteolytic activation of Semliki forest virus. J Virol 77:2981–2989

    PubMed  CAS  Google Scholar 

  46. Krejbich-Trotot P, Denizotm M, Hourau JJ et al (2011) Chikungunya virus mobilizes the apoptotic machinery to invade host cell defenses. FASEB J 25(1):314–325

    PubMed  CAS  Google Scholar 

  47. Dhanwani R, Khan M, Alam SI, Rao PVL, Parida M (2011) Differential proteome analysis of chikungunya virus infected new-born mice tissues reveal implication of stress, inflammatory and apoptotic pathways in disease pathogenesis. Proteomics 11:1936–1951

    PubMed  CAS  Google Scholar 

  48. Bouraï M, Lucas-Hourani M, Gad HH et al (2012) Mapping of chikungunya virus interactions with host proteins identified nsP2 as a highly connected viral component. J Virol 86(6):3121–3133

    PubMed  Google Scholar 

  49. Foss JJ, Domeradzka NE, Baggen J, Geertsema C, Flipse J, Vlak JM, Pijlman GP (2012) Chikungunya virus nsP3 blocks stress granule assembly by recruitment of G3BP into cytoplasmic foci. J Virol 86(19):10873–10879

    Google Scholar 

  50. Salvador B, Zhou Y, Michault A, Muench MO, Simmons G (2009) Characterization of chikungunya pseudotyped viruses: identification of refractory cell lines and demonstration of cellular tropism differences mediated by mutations in E1 glycoprotein. Virology 393:33–41

    PubMed  CAS  Google Scholar 

  51. Leung JYS, Ng MML, Chu JJH (2011) Replication of alphaviruses: a review on the entry process of alphaviruses into cells. Adv Virol 24:9640

    Google Scholar 

  52. Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG (1993) hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem 62:289–321

    PubMed  CAS  Google Scholar 

  53. Shaw ML, Stone KL, Colangelo CM, Gulcicek EE, Palese P (2008) Cellular proteins in influenza virus particles. PLoS Path 4:e1000085

    Google Scholar 

  54. Thangamani S, Higgs S, Ziegler S, Vanlandingham D, Tesh R, Wikel S (2010) Host immune response to mosquito-transmitted chikungunya virus differs from that elicited by needle inoculated virus. PLoS One 5(8):e12137

    PubMed  Google Scholar 

  55. Schmid D, Munz C (2007) Innate and adaptive immunity through autophagy. Immunity 27(1):11–21

    PubMed  CAS  Google Scholar 

  56. Joubert PE, Werneke SW, de la Calle C et al (2012) Chikungunya virus-induced autophagy delays caspase dependent cell death. J Exp Med 209:1029–1047

    PubMed  CAS  Google Scholar 

  57. Dengjel J, Schoor O, Fischer R et al (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA 102:7922–7927

    PubMed  CAS  Google Scholar 

  58. English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippé R, Desjardins M (2009) Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol 10:480–487

    PubMed  CAS  Google Scholar 

  59. Uhl M, Kepp O, Jusforgues-Saklani H, Vicencio JM, Kroemer G, Albert ML (2009) Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death Differ 16:991–1005

    PubMed  CAS  Google Scholar 

  60. Crotzer VL, Blum JS (2010) Autophagy and adaptive immunity. Immunology 131:9–17

    PubMed  CAS  Google Scholar 

  61. Jackson WT, Giddings TH, Taylor MP et al (2005) Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3(5):e156

    PubMed  Google Scholar 

  62. Prentice E, Jerome WG, Yoshimori T et al (2004) Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem 279(11):10136–10141

    PubMed  CAS  Google Scholar 

  63. Lee YR, Lei HY, Liu MT et al (2008) Autophagic machinery activated by dengue virus enhances virus replication. Virology 374(2):240–248

    PubMed  CAS  Google Scholar 

  64. Wong J, Zhang J, Si X et al (2008) Autophagosome supports coxsackie virus B3 replication in host cells. J Virol 82(18):9143–9153

    PubMed  CAS  Google Scholar 

  65. Krejbich-Trotot P, Gay B, Li-Pat-Yuen G et al (2011) Chikungunya triggers an autophagic process which promotes viral replication. Virol J 8:432

    PubMed  CAS  Google Scholar 

  66. Thorburn A (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13:1–9

    PubMed  CAS  Google Scholar 

  67. Djavaheri-Mergny M, Maiuri MC, Kroemer G (2010) Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene 29:1717–1719

    PubMed  CAS  Google Scholar 

  68. Kang R, Zeh HJ, Lotze MT, Tang D (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18:571–580

    PubMed  CAS  Google Scholar 

  69. Lee AH, Iwakoshi NN, Glimcher LH (2003) XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448–7459

    PubMed  CAS  Google Scholar 

  70. McGuckin MA, Eri RD, Das I, Lourie R, Florin TH (2010) ER stress and the unfolded protein response in intestinal inflammation. Am J Physiol Gastrointest Liver Physiol 298:G820–G832

    PubMed  CAS  Google Scholar 

  71. Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287:664–666

    PubMed  CAS  Google Scholar 

  72. Cataldi A (2010) Cell responses to oxidative stressors. Curr Pharm Des 16:1387–1395

    PubMed  CAS  Google Scholar 

  73. Djavaheri-Mergny M, Amelotti M, Mathieu J, Besançon F, Bauvy C, Codogno P (2007) Regulation of autophagy by NFkappaB transcription factor and reactives oxygen species. Autophagy 3:390–392

    PubMed  CAS  Google Scholar 

  74. Filomeni G, Desideri E, Cardaci S, Rotilio G, Ciriolo MR (2010) Under the ROS thiol network is the principal suspect for autophagy commitment. Autophagy 6:999–1005

    PubMed  CAS  Google Scholar 

  75. Guo WJ, Ye SS, Cao N, Huang J, Gao J, Chen QY (2010) ROS mediated autophagy was involved in cancer cell death induced by novel copper(II) complex. Exp Toxicol Pathol 62:577–582

    PubMed  CAS  Google Scholar 

  76. Alexander A, Cai SL, Kim J et al (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA 107:4153–4158

    PubMed  CAS  Google Scholar 

  77. Alexander A, Kim J, Walker CL (2010) ATM engages the TSC2/ mTORC1 signaling node to regulate autophagy. Autophagy 6:672–673

    PubMed  Google Scholar 

  78. Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35

    PubMed  CAS  Google Scholar 

  79. Thomson AW, Turnquist HR, Raimondi G (2009) Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 9:324–337

    PubMed  CAS  Google Scholar 

  80. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    PubMed  CAS  Google Scholar 

  81. Kurokawa M, Kornbluth S (2009) Caspases and kinases in a death grip. Cell 138:838–854

    PubMed  CAS  Google Scholar 

  82. Wilson NS, Dixit V, Ashkenazi A (2009) Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 10:348–355

    PubMed  CAS  Google Scholar 

  83. Kurokawa M, Kornbluth S (2010) Stalling in mitosis and releasing the apoptotic brake. EMBO J 29:2255–2257

    PubMed  CAS  Google Scholar 

  84. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    PubMed  CAS  Google Scholar 

  85. Dhanwani R, Khan M, Bhaskar ASB et al (2012) Characterization of chikungunya virus infection in human neuroblastoma SH-SY5Y cells: role of apoptosis in neuronal cell death. Virus Res 163:563–572

    PubMed  CAS  Google Scholar 

  86. Gorchakov R, Frolova E, Frolo I (2005) Inhibition of transcription and translation in Sindbis virus infected cells. J Virol 79:9397–9409

    PubMed  CAS  Google Scholar 

  87. Tamm K, Merits A, Sarand I (2008) Mutations in nuclear localization signal of nsP2 influence RNA synthesis, protein expression and cytotoxicity of Semliki forest virus. J Gen Virol 89:676–686

    PubMed  CAS  Google Scholar 

  88. Garmashova N, Gorchakov R, Frolova E, Frolov I (2006) Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription. J Virol 80:5686–5696

    PubMed  CAS  Google Scholar 

  89. Fazakerley JK, Boyd A, Mikkola ML, Karriainen L (2002) A single amino acid change in the nuclear localization sequence of the nsP2 protein affects the neurovirulance of Semliki forest virus. J Virol 76:392–396

    PubMed  CAS  Google Scholar 

  90. Inglis SC (1982) Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and herpes simplex virus. Mol Cell Biol 2(12):1644–1648

    PubMed  CAS  Google Scholar 

  91. Beloso A, Martinez C, Valcarcel J, Santaren JF, Ortin J (1992) Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff. J Gen Virol 73:575–581

    PubMed  CAS  Google Scholar 

  92. Lindquist ME, Mainou BA, Dermody TS, Crowe JE Jr (2011) Activation of protein kinase R is required for induction of stress granule by respiratory syncytial virus but dispensable for viral replication. Virology 413:103–110

    PubMed  CAS  Google Scholar 

  93. McInerney GM, Kedersha NL, Kaufman RJ, Anderson P, Liljestrom P (2005) Importance of eIF2α phosphorylation and stress granule assembly in alphavirus translation regulation. Mol Biol Cell 16:3753–3763

    PubMed  CAS  Google Scholar 

  94. Ventoso I, Sanz MA, Molina S, Berlanga JJ, Carrasco L, Esteban M (2006) Translational resistance of late alphavirus mRNA to eIF2α phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR. Genes Dev 20:87–100

    PubMed  CAS  Google Scholar 

  95. Stetson DB, Medzhitov R (2006) Type I interferons in host defense. Immunity 25:373–381

    PubMed  CAS  Google Scholar 

  96. Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F, Rudnicka D et al (2007) Characterization of reemerging chikungunya virus. PLoS Path 3:e89

    Google Scholar 

  97. Her Z, Malleret B, Chan M et al (2010) Active infection of human blood monocytes by chikungunya virus triggers an innate immune response. J Immunol 184:5903–5913

    PubMed  CAS  Google Scholar 

  98. Schilte C, Couderc T, Chretien F et al (2010) Type I IFN controls chikungunya virus via its action on nonhematopoietic cells. J Exp Med 207:429–442

    PubMed  CAS  Google Scholar 

  99. Werneke SW, Schilte C, Rohatgi A et al (2011) ISG15 is critical in the control of chikungunya virus infection independent of UbE1L mediated conjugation. PLoS Pathog 7:e1002322

    PubMed  CAS  Google Scholar 

  100. Ng LFP, Chow A, Sun YJ et al (2009) IL-1beta, IL-6, and RANTES as biomarkers of chikungunya severity. PLoS ONE 4:e4261

    PubMed  Google Scholar 

  101. Broz P, Monack DM (2011) Molecular mechanisms of inflammasome activation during microbial infections. Immunol Rev 243:174–190

    PubMed  CAS  Google Scholar 

  102. Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA (2011) Pattern recognition receptors and the innate immune response to viral infection. Viruses 3:920–940

    PubMed  CAS  Google Scholar 

  103. Kumar H, Kawai T, Akira S (2011) Pathogen recognition by the innate immune system. Int Rev Immunol 30:16–34

    PubMed  CAS  Google Scholar 

  104. Bowie AG, Unterholzner L (2008) Viral evasion and subversion of pattern-recognition receptor signalling. Nat Rev Immunol 8:911–922

    PubMed  CAS  Google Scholar 

  105. Carty M, Bowie AG (2010) Recent insights into the role of toll-like receptors in viral infection. Clin Exp Immunol 161:397–406

    PubMed  CAS  Google Scholar 

  106. Hiscott J, Lin R, Nakhaei P, Paz S (2006) Master-CARD: a priceless link to innate immunity. Trends Mol Med 12:53–56

    PubMed  CAS  Google Scholar 

  107. Loo YM, Gale M (2011) Immune signaling by RIG-Ilike receptors. Immunity 34:680–692

    PubMed  CAS  Google Scholar 

  108. White LK, Sali T, Alvarado D et al (2011) Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff. J Virol 85:606–620

    PubMed  CAS  Google Scholar 

  109. Takaoka A, Yanai H (2006) Interferon signaling network in innate defense. Cell Microbiol 8(6):907–922

    PubMed  CAS  Google Scholar 

  110. Fros JJ, Liu WJ, Prow NA et al (2010) Chikungunya virus nonstructural protein 2 inhibits type I/II interferon stimulated JAK-STAT signaling. J Virol 84:10877–10887

    PubMed  CAS  Google Scholar 

  111. Couderc T, Chrétien F, Schilte C et al (2008) A mouse model for chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Path 4:e29

    Google Scholar 

  112. Akahata W, Yang ZY, Andersen H et al (2010) A VLP vaccine for epidemic chikungunya virus protects nonhuman primates against infection. Nat Med 16(3):334–338

    PubMed  CAS  Google Scholar 

  113. AbuBakar S, Sam IC, Wong PF, MatRahim N, Hooi PS, Roslan N (2007) Reemergence of endemic chikungunya, Malaysia. Emer Infect Dis 13(1):147–149

    Google Scholar 

  114. Antar AA, Konopka JL, Campbell JA et al (2009) Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus. Cell Host Microbe 5(1):59–71

    PubMed  CAS  Google Scholar 

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Acknowledgment

This work was funded by a research grant from the Department of Biotechnology, Government of India (Grant no. BT/PR11162/MED/29/97/2008).

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Correspondence to Sanjay Gupta.

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Rana, J., Sreejith, R., Gulati, S. et al. Deciphering the host-pathogen protein interface in chikungunya virus-mediated sickness. Arch Virol 158, 1159–1172 (2013). https://doi.org/10.1007/s00705-013-1602-1

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