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Real-Time Whole-Body Visualization of Chikungunya Virus Infection and Host Interferon Response in Zebrafish

DOI: 10.1371/journal.ppat.1003619

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Abstract:

Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ~14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN) response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus.

References

[1]  Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT (2012) Chikungunya: a re-emerging virus. Lancet 379: 662–671. doi: 10.1016/s0140-6736(11)60281-x
[2]  Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, et al. (2006) Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med 3: e263. doi: 10.1371/journal.pmed.0030263
[3]  Tsetsarkin K, Higgs S, McGee CE, De Lamballerie X, Charrel RN, et al. (2006) Infectious clones of Chikungunya virus (La Reunion isolate) for vector competence studies. Vector Borne Zoonotic Dis 6: 325–337. doi: 10.1089/vbz.2006.6.325
[4]  de Lamballerie X, Leroy E, Charrel RN, Ttsetsarkin K, Higgs S, et al. (2008) Chikungunya virus adapts to tiger mosquito via evolutionary convergence: a sign of things to come? Virol J 5: 33. doi: 10.1186/1743-422x-5-33
[5]  Tsetsarkin KA, Weaver SC (2011) Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence. PLoS Pathog 7: e1002412. doi: 10.1371/journal.ppat.1002412
[6]  Medlock JM, Hansford KM, Schaffner F, Versteirt V, Hendrickx G, et al. (2012) A review of the invasive mosquitoes in Europe: ecology, public health risks, and control options. Vector Borne Zoonotic Dis 12: 435–447. doi: 10.1089/vbz.2011.0814
[7]  Vega-Rua A, Zouache K, Caro V, Diancourt L, Delaunay P, et al. (2013) High efficiency of temperate Aedes albopictus to transmit chikungunya and dengue viruses in the Southeast of France. PLoS One 8: e59716. doi: 10.1371/journal.pone.0059716
[8]  Schwartz O, Albert ML (2010) Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol 8: 491–500. doi: 10.1038/nrmicro2368
[9]  Dupuis-Maguiraga L, Noret M, Brun S, Le Grand R, Gras G, et al. (2012) Chikungunya disease: infection-associated markers from the acute to the chronic phase of arbovirus-induced arthralgia. PLoS Negl Trop Dis 6: e1446. doi: 10.1371/journal.pntd.0001446
[10]  Suhrbier A, Jaffar-Bandjee MC, Gasque P (2012) Arthritogenic alphaviruses–an overview. Nat Rev Rheumatol 8: 420–429. doi: 10.1038/nrrheum.2012.64
[11]  Lum FM, Teo TH, Lee WW, Kam YW, Renia L, et al. (2013) An Essential Role of Antibodies in the Control of Chikungunya Virus Infection. J Immunol 190: 6295–6302. doi: 10.4049/jimmunol.1300304
[12]  Ozden S, Huerre M, Riviere JP, Coffey LL, Afonso PV, et al. (2007) Human muscle satellite cells as targets of Chikungunya virus infection. PLoS One 2: e527. doi: 10.1371/journal.pone.0000527
[13]  Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F, et al. (2007) Characterization of reemerging chikungunya virus. PLoS Pathog 3: e89. doi: 10.1371/journal.ppat.0030089
[14]  Gerardin P, Barau G, Michault A, Bintner M, Randrianaivo H, et al. (2008) Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Reunion. PLoS Med 5: e60. doi: 10.1371/journal.pmed.0050060
[15]  Economopoulou A, Dominguez M, Helynck B, Sissoko D, Wichmann O, et al. (2009) Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Reunion. Epidemiol Infect 137: 534–541. doi: 10.1017/s0950268808001167
[16]  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. doi: 10.1002/rmv.606
[17]  Das T, Jaffar-Bandjee MC, Hoarau JJ, Krejbich Trotot P, Denizot M, et al. (2010) Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus. Prog Neurobiol 91: 121–129. doi: 10.1016/j.pneurobio.2009.12.006
[18]  Couderc T, Chretien F, Schilte C, Disson O, Brigitte M, et al. (2008) A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog 4: e29. doi: 10.1371/journal.ppat.0040029
[19]  Labadie K, Larcher T, Joubert C, Mannioui A, Delache B, et al. (2010) Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages. J Clin Invest 120: 894–906. doi: 10.1172/jci40104
[20]  Schilte C, Couderc T, Chretien F, Sourisseau M, Gangneux N, et al. (2010) Type I IFN controls chikungunya virus via its action on nonhematopoietic cells. J Exp Med 207: 429–442. doi: 10.1084/jem.20090851
[21]  Gardner J, Anraku I, Le TT, Larcher T, Major L, et al. Chikungunya virus arthritis in adult wild-type mice. J Virol 84: 8021–8032. doi: 10.1128/jvi.02603-09
[22]  Tobin DM, May RC, Wheeler RT (2012) Zebrafish: a see-through host and a fluorescent toolbox to probe host-pathogen interaction. PLoS Pathog 8: e1002349. doi: 10.1371/journal.ppat.1002349
[23]  Lieschke GJ, Oates AC, Crowhurst MO, Ward AC, Layton JE (2001) Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish. Blood 98: 3087–3096. doi: 10.1182/blood.v98.10.3087
[24]  Le Guyader D, Redd MJ, Colucci-Guyon E, Murayama E, Kissa K, et al. (2008) Origins and unconventional behavior of neutrophils in developing zebrafish. Blood 111: 132–141. doi: 10.1182/blood-2007-06-095398
[25]  Zou J, Tafalla C, Truckle J, Secombes CJ (2007) Identification of a second group of type I IFNs in fish sheds light on IFN evolution in vertebrates. J Immunol 179: 3859–3871. doi: 10.4049/jimmunol.179.6.3859
[26]  Aggad D, Mazel M, Boudinot P, Mogensen KE, Hamming OJ, et al. (2009) The two groups of zebrafish virus-induced interferons signal via distinct receptors with specific and shared chains. J Immunol 183: 3924–3931. doi: 10.4049/jimmunol.0901495
[27]  Hamming OJ, Lutfalla G, Levraud JP, Hartmann R (2011) Crystal structure of Zebrafish interferons I and II reveals conservation of type I interferon structure in vertebrates. J Virol 85: 8181–8187. doi: 10.1128/jvi.00521-11
[28]  Levraud JP, Boudinot P, Colin I, Benmansour A, Peyrieras N, et al. (2007) Identification of the zebrafish IFN receptor: implications for the origin of the vertebrate IFN system. J Immunol 178: 4385–4394. doi: 10.4049/jimmunol.178.7.4385
[29]  Weston J, Villoing S, Bremont M, Castric J, Pfeffer M, et al. (2002) Comparison of two aquatic alphaviruses, salmon pancreas disease virus and sleeping disease virus, by using genome sequence analysis, monoclonal reactivity, and cross-infection. J Virol 76: 6155–6163. doi: 10.1128/jvi.76.12.6155-6163.2002
[30]  Forrester NL, Palacios G, Tesh RB, Savji N, Guzman H, et al. (2012) Genome-scale phylogeny of the alphavirus genus suggests a marine origin. J Virol 86: 2729–2738. doi: 10.1128/jvi.05591-11
[31]  Durbin R, Kane A, Stollar V (1991) A mutant of Sindbis virus with altered plaque morphology and a decreased ratio of 26 S:49 S RNA synthesis in mosquito cells. Virology 183: 306–312. doi: 10.1016/0042-6822(91)90143-y
[32]  Phelan PE, Pressley ME, Witten PE, Mellon MT, Blake S, et al. (2005) Characterization of snakehead rhabdovirus infection in zebrafish (Danio rerio). J Virol 79: 1842–1852. doi: 10.1128/jvi.79.3.1842-1852.2005
[33]  Lopez-Munoz A, Roca FJ, Sepulcre MP, Meseguer J, Mulero V (2010) Zebrafish larvae are unable to mount a protective antiviral response against waterborne infection by spring viremia of carp virus. Dev Comp Immunol 34: 546–552. doi: 10.1016/j.dci.2009.12.015
[34]  Ludwig M, Palha N, Torhy C, Briolat V, Colucci-Guyon E, et al. (2011) Whole-body analysis of a viral infection: vascular endothelium is a primary target of infectious hematopoietic necrosis virus in zebrafish larvae. PLoS Pathog 7: e1001269. doi: 10.1371/journal.ppat.1001269
[35]  Rudd PA, Wilson J, Gardner J, Larcher T, Babarit C, et al. (2012) Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock. J Virol 86: 9888–9898. doi: 10.1128/jvi.00956-12
[36]  Schilte C, Buckwalter MR, Laird ME, Diamond MS, Schwartz O, et al. (2012) Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection. J Immunol 188: 2967–2971. doi: 10.4049/jimmunol.1103185
[37]  Brannon MK, Davis JM, Mathias JR, Hall CJ, Emerson JC, et al. (2009) Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos. Cell Microbiol 11: 755–768. doi: 10.1111/j.1462-5822.2009.01288.x
[38]  Davison JM, Akitake CM, Goll MG, Rhee JM, Gosse N, et al. (2007) Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish. Dev Biol 304: 811–824. doi: 10.1016/j.ydbio.2007.01.033
[39]  Liongue C, Hall CJ, O'Connell BA, Crosier P, Ward AC (2009) Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration. Blood 113: 2535–2546. doi: 10.1182/blood-2008-07-171967
[40]  Hall CJ, Flores MV, Oehlers SH, Sanderson LE, Lam EY, et al. (2012) Infection-responsive expansion of the hematopoietic stem and progenitor cell compartment in zebrafish is dependent upon inducible nitric oxide. Cell Stem Cell 10: 198–209. doi: 10.1016/j.stem.2012.01.007
[41]  Curado S, Ober EA, Walsh S, Cortes-Hernandez P, Verkade H, et al. (2010) The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model. Dis Model Mech 3: 486–495.
[42]  Ziegler SA, Lu L, da Rosa AP, Xiao SY, Tesh RB (2008) An animal model for studying the pathogenesis of chikungunya virus infection. Am J Trop Med Hyg 79: 133–139.
[43]  Wang E, Volkova E, Adams AP, Forrester N, Xiao SY, et al. (2008) Chimeric alphavirus vaccine candidates for chikungunya. Vaccine 26: 5030–5039. doi: 10.1016/j.vaccine.2008.07.054
[44]  Sun F, Zhang YB, Liu TK, Gan L, Yu FF, et al. (2010) Characterization of fish IRF3 as an IFN-inducible protein reveals evolving regulation of IFN response in vertebrates. J Immunol 185: 7573–7582. doi: 10.4049/jimmunol.1002401
[45]  Takauji R, Iho S, Takatsuka H, Yamamoto S, Takahashi T, et al. (2002) CpG-DNA-induced IFN-alpha production involves p38 MAPK-dependent STAT1 phosphorylation in human plasmacytoid dendritic cell precursors. J Leukoc Biol 72: 1011–1019.
[46]  Pulverer JE, Rand U, Lienenklaus S, Kugel D, Zietara N, et al. (2010) Temporal and spatial resolution of type I and III interferon responses in vivo. J Virol 84: 8626–8638. doi: 10.1128/jvi.00303-10
[47]  Hayashi F, Means TK, Luster AD (2003) Toll-like receptors stimulate human neutrophil function. Blood 102: 2660–2669. doi: 10.1182/blood-2003-04-1078
[48]  Tamassia N, Le Moigne V, Rossato M, Donini M, McCartney S, et al. (2008) Activation of an immunoregulatory and antiviral gene expression program in poly(I:C)-transfected human neutrophils. J Immunol 181: 6563–6573. doi: 10.4049/jimmunol.181.9.6563
[49]  Drescher B, Bai F (2013) Neutrophil in viral infections, friend or foe? Virus Res 171: 1–7. doi: 10.1016/j.virusres.2012.11.002
[50]  Jenne CN, Wong CHY, Zemp FJ, McDonald B, Rahman MM, et al. (2013) Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe 13: 169–180. doi: 10.1016/j.chom.2013.01.005
[51]  Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, et al. (2012) Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 12: 109–116. doi: 10.1016/j.chom.2012.05.015
[52]  Palic D, Andreasen CB, Ostojic J, Tell RM, Roth JA (2007) Zebrafish (Danio rerio) whole kidney assays to measure neutrophil extracellular trap release and degranulation of primary granules. J Immunol Methods 319: 87–97. doi: 10.1016/j.jim.2006.11.003
[53]  Colucci-Guyon E, Tinevez JY, Renshaw SA, Herbomel P (2011) Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils engulf only surface-associated microbes. J Cell Sci 124: 3053–3059. doi: 10.1242/jcs.082792
[54]  Yang CT, Cambier CJ, Davis JM, Hall CJ, Crosier PS, et al. (2012) Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe 12: 301–312. doi: 10.1016/j.chom.2012.07.009
[55]  Navarini AA, Recher M, Lang KS, Georgiev P, Meury S, et al. (2006) Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses. Proc Natl Acad Sci U S A 103: 15535–15539. doi: 10.1073/pnas.0607325103
[56]  Ronneseth A, Pettersen EF, Wergeland HI (2006) Neutrophils and B-cells in blood and head kidney of Atlantic salmon (Salmo salar L.) challenged with infectious pancreatic necrosis virus (IPNV). Fish Shellfish Immunol 20: 610–620. doi: 10.1016/j.fsi.2005.08.004
[57]  Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, et al. (2011) Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor. J Infect Dis 203: 149–157. doi: 10.1093/infdis/jiq042
[58]  Cuzzocrea S, Chatterjee PK, Mazzon E, Dugo L, De Sarro A, et al. (2002) Role of induced nitric oxide in the initiation of the inflammatory response after postischemic injury. Shock 18: 169–176. doi: 10.1097/00024382-200208000-00014
[59]  Genovese T, Cuzzocrea S, Di Paola R, Failla M, Mazzon E, et al. (2005) Inhibition or knock out of inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury. Respir Res 6: 58.
[60]  Zeidler PC, Millecchia LM, Castranova V (2004) Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation. Toxicol Appl Pharmacol 195: 45–54. doi: 10.1016/j.taap.2003.10.005
[61]  Orvedahl A, MacPherson S, Sumpter R Jr, Talloczy Z, Zou Z, et al. (2010) Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7: 115–127. doi: 10.1016/j.chom.2010.01.007
[62]  Stetson DB, Medzhitov R (2006) Type I interferons in host defense. Immunity 25: 373–381. doi: 10.1016/j.immuni.2006.08.007
[63]  Jeong JY, Kwon HB, Ahn JC, Kang D, Kwon SH, et al. (2008) Functional and developmental analysis of the blood-brain barrier in zebrafish. Brain Res Bull 75: 619–628. doi: 10.1016/j.brainresbull.2007.10.043
[64]  Murooka TT, Deruaz M, Marangoni F, Vrbanac VD, Seung E, et al. (2012) HIV-infected T cells are migratory vehicles for viral dissemination. Nature 490: 283–287. doi: 10.1038/nature11398
[65]  Sewald X, Gonzalez DG, Haberman AM, Mothes W (2012) In vivo imaging of virological synapses. Nat Commun 3: 1320. doi: 10.1038/ncomms2338
[66]  Hickman HD, Reynoso GV, Ngudiankama BF, Rubin EJ, Magadán JG, et al. (2013) Anatomically restricted synergistic antiviral activities of innate and adaptive immune cells in the skin. Cell Host Microbe 13: 155–168. doi: 10.1016/j.chom.2013.01.004
[67]  Westerfield M (2000) The Zebrafish Book: A guide for the laboratory use of zebrafish (Danio rerio). Corvallis: University of Oregon Press.
[68]  Levraud JP, Colucci-Guyon E, Redd MJ, Lutfalla G, Herbomel P (2008) In vivo analysis of zebrafish innate immunity. Methods Mol Biol 415: 337–363. doi: 10.1007/978-1-59745-570-1_20
[69]  Traver D, Paw BH, Poss KD, Penberthy WT, Lin S, et al. (2003) Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat Immunol 4: 1238–1246. doi: 10.1038/ni1007
[70]  Park HC, Kim CH, Bae YK, Yeo SY, Kim SH, et al. (2000) Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons. Dev Biol 227: 279–293. doi: 10.1006/dbio.2000.9898
[71]  Bernardos RL, Raymond PA (2006) GFAP transgenic zebrafish. Gene Expr Patterns 6: 1007–1013. doi: 10.1016/j.modgep.2006.04.006
[72]  Dong PD, Munson CA, Norton W, Crosnier C, Pan X, et al. (2007) Fgf10 regulates hepatopancreatic ductal system patterning and differentiation. Nat Genet 39: 397–402. doi: 10.1038/ng1961
[73]  Renshaw SA, Loynes CA, Trushell DM, Elworthy S, Ingham PW, et al. (2006) A transgenic zebrafish model of neutrophilic inflammation. Blood 108: 3976–3978. doi: 10.1182/blood-2006-05-024075
[74]  Ellett F, Pase L, Hayman JW, Andrianopoulos A, Lieschke GJ (2011) mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish. Blood 117: e49–56. doi: 10.1182/blood-2010-10-314120
[75]  Suster ML, Kikuta H, Urasaki A, Asakawa K, Kawakami K (2009) Transgenesis in zebrafish with the tol2 transposon system. Methods Mol Biol 561: 41–63. doi: 10.1007/978-1-60327-019-9_3
[76]  Ellett F, Lieschke GJ (2012) Computational quantification of fluorescent leukocyte numbers in zebrafish embryos. Methods Enzymol 506: 425–435. doi: 10.1016/b978-0-12-391856-7.00046-9
[77]  Svoboda KR, Linares AE, Ribera AB (2001) Activity regulates programmed cell death of zebrafish Rohon-Beard neurons. Development 128: 3511–3520.
[78]  Greiser-Wilke I, Moenning V, Kaaden OR, Figueiredo LT (1989) Most alphaviruses share a conserved epitopic region on their nucleocapsid protein. J Gen Virol 70 (Pt 3) 743–748. doi: 10.1099/0022-1317-70-3-743
[79]  Covassin L, Amigo JD, Suzuki K, Teplyuk V, Straubhaar J, et al. (2006) Global analysis of hematopoietic and vascular endothelial gene expression by tissue specific microarray profiling in zebrafish. Dev Biol 299: 551–562. doi: 10.1016/j.ydbio.2006.08.020
[80]  Thisse C, Thisse B (2008) High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 3: 59–69. doi: 10.1038/nprot.2007.514

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