- Open Access
Transcriptional profiling of Drosophila S2 cells in early response to Drosophila C virus
© Zhu et al.; licensee BioMed Central Ltd. 2013
- Received: 18 April 2013
- Accepted: 24 June 2013
- Published: 27 June 2013
The innate immune response like phagocytosis, encapsulation and antimicrobial peptide (AMP) production often occur in the early stage of host-pathogen interactions in Drosophila melanogaster. To investigate the Drosophila early immune response to Drosophila C virus, we characterized the DCV infection-response transcriptome of Drosophila Schneider 2 (S2) cells at one hour post inoculation.
The total RNA was extracted from treated S2 cells by using Trizol reagent and then analyzed by CapitalBio Corp for Drosophila GeneChip (Affymetrix) assay. Then the results of signaling pathway and protein interaction about these genes were analyzed by MAS 3.0 software.
Most significantly affected genes (656 genes) by DCV infection were regulated as the same way in inactivated DCV treatment, but inactivated white spot syndrome virus (WSSV) showed a different transcriptome. DCV infection up-regulated the expression levels of 275 genes and down-regulated that of 442 genes significantly and some affected genes were related to phagocytosis. DCV infection activated the JAK/STAT pathway by 1 hour post incubation. The Imd pathway was activated and transcriptional induction of antimicrobial peptides (AMPs) from this pathway was enhanced by 1 hour post incubation. But the Toll pathway was not activated like Imd pathway and the expression levels of AMPs from this pathway was reduced. In addition, most pattern-recognition receptors were inhibited and the antiviral RNAi pathway was not activated in the early stage of DCV infection.
In conclusion, the present study demonstrates that DCV infection may activate phagocytosis, JAK/STAT pathway and Imd pathway in the early host-virus interactions. These results indicate that DCV is capable of activating or inhibiting some immune responses in the host cells and these changes would be vital for virus entry and replication.
- Transcriptional profiling
- Drosophila S2 cells
- Early response
- Drosophila C virus
The innate immune response of Drosophila is governed by numerous signaling pathways that trigger antimicrobial peptide (AMP) production, phagocytosis, melanization, and encapsulation to limit infection after exposure to microbes [1, 2]. Drosophila C virus (DCV) is a non-occluded isometric virus which containing a positive sense RNA genome [3, 4]. DCV is a natural pathogen of the model organism D. melanogaster, making it an ideal model system for studying invertebrate host-virus interactions . The mechanisms of antiviral defense in Drosophila highlight the potential of the D. melanogaster model for studying antiviral innate immunity . It is found that the Imd pathway is involved in the antiviral immune responses of Drosophila[7, 8]. The Toll pathway is required for efficient inhibition of Drosophila X virus replication in Drosophila and constitutive activation of the pathway resulted in decreased viral titer . Recently RNA interference (RNAi) was found to mediate innate antiviral immunity in Drosophila[10–12]. The JAK/STAT signaling pathway is reported to involve in the antiviral response of Drosophila[11–13]. However, many viruses always develop the ability of suppressing or evading host immune response. No evidence for the activation of the Toll, IMD or JAK/STAT pathways was found in D. melanogaster infected with the sigma virus (Rhabdoviridae) . And dengue virus (DENV) may suppress immune responses at early infection stages before activating them at later time points in Aedes aegypti. So it is very necessary to study the early immune response to pathogenic virus in host cells.
White spot syndrome virus (WSSV) is a bacilliform, enveloped double stranded DNA virus that causes viral diseases in shrimp . To investigate early immune responses against DCV, we exposed Drosophila S2 cells to DCV, inactivated DCV (inDCV), and inactivated WSSV (inWSSV). We selected inWSSV as a treatment but not WSSV because WSSV was not phagocytosed by S2 cells like DCV and inDCV and induced very complicated early response. We investigated the transcriptional profile of virus-challenged Drosophila S2 cells using oligonucleotide DNA microarrays to identify the Drosophila early immune response to DCV. This results of this study contribute to the understanding of early immunologic defense responses in invertebrate hosts to viral challenge, and this study paves the way for further experiments which investigate the roles of genes and pathways in antiviral immunity.
Genome-wide analysis of the Drosophila early immune response to DCV
The list of DCV infection affected genes
The number of affected genes
275 up-regulated genes
18w, a, Ald, alpha-Adaptin, alpha-Est1, alphaPS4, alphaPS5, AnnIX, alphaTub84D, aPKC, Asator, Ast, Atpalpha, AttA, AttC, AttD, b, B52, Best1, bnl, brp, bves, CaMKII, Ccn, Cct1, Cdk5, CecB, CecC, CG10011, CG10103, CG10337, CG10581, CG10630, CG10641, CG10657, CG10702, CG10962, CG1124, CG11353, CG11671, CG11779, CG11790, CG11791, CG11825, CG11897, CG12014, CG12054, CG12112, CG12290, CG12418, CG12477, CG12883, CG12896, CG13078, CG13196, CG13248, CG13335, CG1340, CG13482, CG14015, CG14085, CG14322, CG14340, CG14545, CG14567, CG14801, CG14879, CG15097, CG15308, CG15543, CG15673, CG1600, CG16717, CG16718, CG16833, CG17599, CG17660, CG17681, CG18528, CG18557, CG18643, CG18769, CG30108, CG30115, CG30281, CG30421, CG30466, CG30502, CG31012, CG31323, CG31324, CG31431, CG31522, CG31523, CG3168, CG31778, CG32048, CG32066, CG32170, CG32206, CG32207, CG32313, CG32512, CG32982, CG33099, CG3348, CG34330, CG34349, CG34360, CG34383, CG34404, CG3788, CG3884, CG42327, CG42348, CG4455, CG4570, CG4629, CG4726, CG5174, CG5246, CG5346, CG5535, CG5758, CG5919, CG6051, CG6125, CG6231, CG6330, CG6357, CG6498, CG6767, CG7056, CG7251, CG7510, CG7720, CG7778, CG7794, CG7816, CG7841, CG7888, CG8008, CG8046, CG8177, CG9119, CG9222, CG9238, CG9312, CG9626, CG9641, CG9663, CG9812, CG9932, cher, chn, chrb, Cortactin, Cpr67Fa1, Csk, Cyp4g1, DAAM, dally, Dhap-at, drl, Ets21C, ewg, fra, Gadd45, GlcAT-S, Gli, Gp150, Gr94a, gsb, h, Hip1, Hsp22, Hsp70Aa, Hsp70Ba, Hsp70Bc, ifc, ImpL2, ImpL3, insc, inx2, Irk3, jar, JhI-21, Jupiter, kay, kel, KP78b, KrT95D, lcs, Lerp, Lis-1, Lmpt, loco, LpR2, Luna, Mctp, Mf, Mmp1, moody, Mpk2, mthl2, Mtk, MtnA, Myo28B1, Myo31DF, mys, nahoda, nau, nes, Nhe3, nkd, Nrt, Oatp30B, Obp44a, Or19a, ovo, Pabp2, pain, Pak, path, Pde8, Phk-3, pirk, Pka-C3, PKD, pot, ppk10, Prx2540-2, puc, Pvf2, Rel, Rep, Rgn, RhoGEF3, RhoL, RN-tre, rogdi, RpS5b, rtGEF, scarface, sdk, shn, SIP3, slgA, Socs36E, Sox14, spir, Stam, stv, Su(dx), tamo, Thor, tmod, Tom34, Trc8, Tsp, Tsp42Eg, tty, Ugt36Bb, upd2, upd3, vfl, viaf, vir-1, Vrp1, WASp, wun, wun2, yellow-b, zfh1, zpg
442 down-regulated genes
Ac13E, Ac76E, Acer, Acox57D-d, Act79B, Adk3, Amph, Ance-5, arg, armi, Atet, att-ORFA, aub, Bc, Best4, betaTub97EF, bgm, bmm, bt, by, Cad96Ca, CG10026, CG10073, CG10126, CG10131, CG10184, CG10205, CG10249, CG10336, CG10469, CG10479, CG10512, CG10550, CG10660, CG10764, CG10863, CG11063, CG11134, CG11147, CG11151, CG11319, CG11347, CG11395, CG11400, CG11638, CG11668, CG11686, CG11739, CG11943, CG12140, CG12262, CG12340, CG12512, CG12702, CG12744, CG12825, CG12970, CG13085, CG13116, CG13377, CG13559, CG13631, CG13641, CG13654, CG13707, CG13794, CG13822, CG13877, CG13897, CG14033, CG14141, CG14215, CG14216, CG14225, CG14511, CG14615, CG14619, CG14629, CG14741, CG14787, CG14803, CG14806, CG14856, CG14872, CG14933, CG14990, CG1503, CG15043, CG15161, CG15202, CG15333, CG15658, CG15739, CG15818, CG15820, CG15917, CG1607, CG1623, CG1628, CG1637, CG1648, CG16700, CG16712, CG16713, CG1674, CG16947, CG1702, CG17029, CG17032, CG17167, CG17270, CG17322, CG17323, CG17350, CG17549, CG17597, CG17839, CG17928, CG18446, CG18522, CG18549, CG18563, CG18622, CG2003, CG2052, CG2444, Cg25C, CG2893, CG30017, CG30069, CG30085, CG30090, CG30104, CG30148, CG30217, CG30269, CG30273, CG30345, CG30359, CG3036, CG30377, CG30460, CG30463, CG30479, CG30492, CG31048, CG31075, CG31145, CG31274, CG31313, CG31326, CG31454, CG31477, CG31601, CG31607, CG31674, CG31675, CG3184, CG31886, CG3191, CG31974, CG31999, CG32017, CG32085, CG32091, CG3224, CG32306, CG32320, CG32354, CG32364, CG3246, CG32582, CG3259, CG32613, CG32647, CG32700, CG32812, CG33225, CG33252, CG33275, CG33465, CG3402, CG34331, CG34398, CG34436, CG3505, CG3635, CG3829, CG3831, CG3857, CG3902, CG40160, CG4019, CG40244, CG41265, CG42259, CG42296, CG42345, CG42358, CG42369, CG42394, CG4250, CG42611, CG4325, CG4351, CG4389, CG4398, CG4484, CG4576, CG4598, CG4615, CG4666, CG4733, CG4928, CG4949, CG5080, CG5167, CG5191, CG5322, CG5381, CG5397, CG5455, CG5707, CG5731, CG5853, CG5895, CG5955, CG5958, CG5973, CG6045, CG6188, CG6199, CG6208, CG6232, CG6289, CG6410, CG6426, CG6639, CG6687, CG6812, CG6836, CG6951, CG7059, CG7083, CG7091, CG7120, CG7149, CG7255, CG7280, CG7320, CG7322, CG7358, CG7458, CG7607, CG7777, CG7781, CG7966, CG7985, CG7995, CG7997, CG8066, CG8080, CG8097, CG8112, CG8157, CG8211, CG8213, CG8353, CG8398, CG8399, CG8451, CG8501, CG8586, CG8668, CG8788, CG9008, CG9098, CG9117, CG9232, CG9331, CG9338 , CG9416, CG9463, CG9505, CG9541, CG9577, CG9616, CG9624, CG9691, CG9973, CG9989, cpo, Cpr49Ac, Cpr65Au, Cpr97Eb, CPTI, CREG, Cyp12c1, Cyp12d1-d, Cyp18a1, Cyp28a5, Cyp28d1, Cyp4ac1, Cyp4d2, Cyp4s3, Cyp6a13, Cyp6a14, Cyp6a21, Cyp9f2, Cyp9h1, Cys, Dh, dj-1beta, DNApol-alpha50, DNaseII, dpp, dpr17, drpr, eater, edl, egr, Ela, fan, fbp, fng, fru, fz2, GLaz, glob1, Glt, grh, GstD4, GstD5, GstD6, GstD7, He, Hil, hoe1, Hr51, Hsp60B, htl, if, ine, Invadolysin, inx3, Irp-1B, Jheh3, Kap-alpha3, l(3)neo38, lectin-24A, lectin-28C, lin-28, Lip4, Lkr, lox, mAcR-60C, mav, mbc, Mcm6, mew, mex1, mspo, Myd88, MYPT-75D, nAcRalpha-30D, Nep4, NetB, Nha2, nimB2, nimB3, nimB4, nimB5, nimC1, nimC2, Oat, Oatp33Ea, Obp18a, Obp99a, Obp99c, obst-A, olf186-M, out, Pde6, Pdk, PGRP-LE, Pka-R2, PNUTS, prc, Prestin, Pxn, pyd, pyd3, qtc, r-cup, rdgB, rg, Rgk1, Rph, Rpt3R, ry, scpr-A, scu, shf, Sip1, Sk1, skpB, sls, sn, snk, Sp212, sqz, Sr-CI, Sry-alpha, stnA, Strn-Mlck, su(r), Sucb, Sur, sut1, Taf12L, TepI, topi, TotA, troll, Tsp29Fa, Tsp2A, Tsp5D, TwdlE, twi, Ubc84D, Ugt35a, Ugt36Bc, Ugt86Dd, Vago, veil, vkg, W, wnd, y, yellow-f2, yellow-h, yip2
Expression profiles of selected important immune genes revolved in early immune response to DCV, inDCV and inWSSV
Gene (GenBank accession number)
Immunity signal transduction
JAK/STAT pathway is involved in antiviral immunity in Drosophila
Toll pathway is involved in early response to Drosophila C virus
Imd pathway is involved in early response to Drosophila C virus
RNAi pathway was not activated in early response to Drosophila C virus
Previous studies have shown that RNA interference played a critical role in the control of viral infections in Drosophila and Ago2, Ars2, Dcr-2 and R2D2 as the core antiviral RNAi machinery [10, 35, 36]. However, the relative expression of Ago1, Ago2, Ars2, Dcr-1, Dcr-2, R2D2 and Drosha, which are important to antiviral RNAi pathway in Drosophila, remained stable in all three experimental groups (data not shown). The antiviral RNAi pathway was not activated in S2 cells by 1 hour post incubation with DCV or inWSSV. Virus infection in Drosophila initiates a specific transcriptional response, including the induction of Vago, a recently identified antiviral molecule that is required to restrict viral replication in flies . In this study, Vago was significantly down-regulated (P<0.01) in all three treatments (Table 2). The data indicate that the antiviral RNAi pathway was not induced in S2 cells at 1 hour post incubation with DCV or inWSSV. Previous studies also showed that DCV encodes a dsRNA-binding protein, DCV-1A, which suppresses RNA silencing in Drosophila[38, 39].
Maintenance of Drosophila S2 cell line and treatment
Drosophila S2 cells were cultivated at 28°C in Schneider’s Drosophila medium (Ivitrogen, USA) supplemented with 10% fetal bovine serum (Gibco, USA). DCV was inoculated in S2 cells at a multiplicity of infection (MOI) of 1 for 4 days and collected for purification as described before . Then S2 cells were infected with purified DCV at a multiplicity of infection (MOI) of 1. DCV at a multiplicity of infection (MOI) of 1 was UV-inactivated by exposure to a total of 12, 000 mJ UV light (5×3 min) as inactivated DCV (inDCV), and then S2 cells were inoculated with UV-inactivated DCV. The WSSV were purified from WSSV-infected shrimp according to the previous methods . The WSSV virions were UV-inactivated by exposure to a total of 12, 000 mJ UV light (5×3 min). Subsequently the inactivated WSSV virions (1 × 107 copies/mL) were inoculated in S2 cells (1 × 106 cells/mL). After one hour, the S2 cells were collected and subjected to oligonucleotide microarray.
Analyses of mRNA expressions with oligonucleotide microarray
The total RNA was extracted from treated S2 cells by using Trizol reagent (Invitrogen, USA) according to the manufacturer’s instructions. The total RNA samples were then analyzed by CapitalBio Corp for Drosophila GeneChip (Affymetrix) assay. And each treatment has 3 biological replicates that were measured by this way. Gene expression analysis was performed by using the Affymetrix (Santa Clara, CA, USA) Drosophila GeneChip, using the laboratory methods in the Affymetrix GeneChip expression manual. Gene expression analysis was performed using triple arrays and triple independent mRNA samples for each treatment. Microarray data were analyzed by using Bio MAS (molecule annotation system) 3.0 software (CapitalBio Corporation, Beijing, China). Using the criterion of cutoff limitation as a fold change ≥ 2 or ≤0.5 and q-value ≤ 5%, differential expression genes were screened and clustered.
Biological pathway analysis
Through array analysis, the commonly altered genes were screened from DCV, and WSSV treatments. The selected genes were further analyzed in the context of Gene Ontology (GO) biological process and Kyoto Encyclopaedia of Genes and Genomes (KEGG) biological pathway. Then the results of signaling pathway and protein interaction about these genes were analyzed by MAS 3.0 software. To reveal the functions of predicted target genes, we used the ontology classification of genes based on gene annotation and summary information available through DAVID (Database for Annotation, Visualization and Integrated Discovery).
Transmission electron microscopy assay
The S2 cells were pelleted and fixed in the fixative containing 2% paraformaldehyde and 2% glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4) for 18 h at room temperature. Each sample was washed three times with 0.1 M sodium cacodylate buffer at room temperature. Then the sample was postfixed with 2% osmium tetroxide in 0.1 M sodium cacodylate buffer with constant rotation for 1h, followed by washes three times using 0.1 M sodium cacodylate buffer at room temperature. The sample was stained with 2% uranyl acetate in 0.2 M sodium acetate buffer (pH 5.2) for 1 h at room temperature and subsequently washed three times with 0.2 M sodium acetate buffer at room temperature. The sample was dehydrated in an ascending acetone series (50, 60, 70, 80, 90, 95, and 100%) and then in 100% propylene oxide for 10 min with constant rotation at room temperature. After infiltration of sample with EMBED 812/Araldite 502 resin at room temperature, sections were prepared in a Reichert Ultracut OMU3 microtome (Leica, Germany) at 100 nm thickness, followed by staining with 2% uranyl acetate/70% methanol. The images were collected on a Hitachi 7650 transmission electron microscope (Hitachi, Japan) operating at 70 kV.
Statistical significance was determined by Student's t-test (two-tailed distribution with a two sample equal variance). P-values of less than 0.05 were considered significant and less than 0.01 were considered very significant.
This work was financially supported by National Natural Science Foundation of China (31001127).
- Hoffmann JA, Reichhart JM: Drosophila innate imunity: an evolutionary perspective. Nat Immunol 2002, 2: 121-126.View ArticleGoogle Scholar
- Hoffmann JA: The immune response of Drosophila . Nature 2002, 12: 33-38.Google Scholar
- Johnson KN, Christian PD: The novel genome organization of the insect picornalike virus Drosophila C virus suggests this virus belongs to a previously undescribed virus family. J Gen Virol 1998, 79: 191-203.PubMedView ArticleGoogle Scholar
- Johnson KN, Christian PD: Molecular characterization of Drosophila C virus isolates. J Invertebr Pathol 1999, 73: 248-254. 10.1006/jipa.1998.4830PubMedView ArticleGoogle Scholar
- Hedges LM, Johnson KN: Induction of host defence responses by Drosophila C virus. J Gen Virol 2008, 89: 1497-1501. 10.1099/vir.0.83684-0PubMedView ArticleGoogle Scholar
- Huszar T, Imler JL: Drosophila viruses and the study of antiviral host-defense. Adv Virus Res 2008, 72: 227-265.PubMedView ArticleGoogle Scholar
- Tanji T, Hu XD, Weber ANR, Ip YT: Toll and IMD Pathways synergistically activate an innate immune response in Drosophila melanogaster . Mol Cell Biol 2007, 27: 4578-4588. 10.1128/MCB.01814-06PubMedPubMed CentralView ArticleGoogle Scholar
- Costa A, Jan E, Sarnow P, Schneider D: The Imd pathway is involved in antiviral immune responses in Drosophila . PLoS One 2009, 4: e7436. 10.1371/journal.pone.0007436PubMedPubMed CentralView ArticleGoogle Scholar
- Zambon RA, Nandakumar M, Vakharia VN, Wu LP: The Toll pathway is important for an antiviral response in Drosophila . Proc Nat Acad Sci USA 2005, 102: 7257-7262. 10.1073/pnas.0409181102PubMedPubMed CentralView ArticleGoogle Scholar
- Saleh MC, Tassetto M, Van Rij RP, Goic B, Gausson V, Berry B, Jacquier C, Antoniewski C, Andino R: Antiviral immunity in Drosophila requires systemic RNA interference spread. Nature 2009, 458: 346-350. 10.1038/nature07712PubMedPubMed CentralView ArticleGoogle Scholar
- Kemp C, Imler JL: Antiviral immunity in Drosophila . Curr Opin Immunol 2009, 21: 3-9. 10.1016/j.coi.2009.01.007PubMedPubMed CentralView ArticleGoogle Scholar
- Sabin LR, Hanna SL, Cherry S: Innate antiviral immunity in Drosophila . Curr Opin Immunol 2010, 22: 4-9. 10.1016/j.coi.2010.01.007PubMedPubMed CentralView ArticleGoogle Scholar
- Dostert C, Jouanguy E, Irving P, Troxler L, Galiana-Arnoux D, Hetru C, Hoffmann JA, Imler JL: The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of Drosophila . Nat Immunol 2005, 6: 946-953.PubMedView ArticleGoogle Scholar
- Carpenter J, Hutter S, Baines JF, Roller J, Saminadin-Peter SS, Parsch J, Jiggins FM: The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae). PLoS One 2009, 4: e6838. 10.1371/journal.pone.0006838PubMedPubMed CentralView ArticleGoogle Scholar
- Ramirez JL, Dimopoulos G: The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae . aegypti strains and against multiple dengue virus serotypes. Dev Comp Imm 2010, 34: 625-629. 10.1016/j.dci.2010.01.006View ArticleGoogle Scholar
- Escobedo Bonilla CM, Alday-Sanz V, Wille M, Sorgeloos P, Pensaert MB, Nauwynck HJ: A review on the morphology, molecular characterization, morphogenesis and pathogenesis of white spot syndrome virus. J Fish Dis 2008, 31: 1-18.PubMedView ArticleGoogle Scholar
- Sim S, Dimopoulos G: Dengue virus inhibits immune responses in Aedes aegypti cells. PLoS One 2010, 5: e10678. 10.1371/journal.pone.0010678PubMedPubMed CentralView ArticleGoogle Scholar
- Wang MH, Marinotti O, James AA, Walker E, Githure J, Yan G: Genome-wide patterns of gene expression during aging in the african malaria vector Anopheles gambiae . PLoS One 2010, 5: e13359. 10.1371/journal.pone.0013359PubMedPubMed CentralView ArticleGoogle Scholar
- Vidal M, Larson DE, Cagan RL: Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis. Dev Cell 2006, 10: 33-44. 10.1016/j.devcel.2005.11.007PubMedView ArticleGoogle Scholar
- Stewart RA, Li DM, Huang H, Xu T: A genetic screen for modifiers of the lats tumor suppressor gene identifies C-terminal Src kinase as a regulator of cell proliferation in Drosophila . Oncogene 2003, 22: 6436-6444. 10.1038/sj.onc.1206820PubMedView ArticleGoogle Scholar
- Pedraza LG, Stewart RA, Li DM, Xu T: Drosophila Src-family kinases function with Csk to regulate cell proliferation and apoptosis. Oncogene 2004, 23: 4754-4762. 10.1038/sj.onc.1207635PubMedView ArticleGoogle Scholar
- Read RD, Bach EA, Cagan RL: Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways. Mol Cell Biol 2004, 24: 6676-6689. 10.1128/MCB.24.15.6676-6689.2004PubMedPubMed CentralView ArticleGoogle Scholar
- Berton G, Mocsai A, Lowell CA: Src and Syk kinases: key regulators of phagocytic cell activation. Trends Immunol 2005, 26: 208-214. 10.1016/j.it.2005.02.002PubMedView ArticleGoogle Scholar
- Majeed M, Caveggion E, Lowell CA, Berton G: Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion. J Leukoc Biol 2001, 70: 801-811.PubMedGoogle Scholar
- Ghigo E, Kartenbeck J, Lien P, Pelkmans L, Capo C, Mege JL, Raoult D: Ameobal pathogen mimivirus infects macrophages through phagocytosis. PLoS Pathog 2008, 4: e1000087. 10.1371/journal.ppat.1000087PubMedPubMed CentralView ArticleGoogle Scholar
- Mercer J, Schelhaas M, Helenius A: Virus entry by endocytosis. Ann Rev Biochem 2010, 79: 803-833. 10.1146/annurev-biochem-060208-104626PubMedView ArticleGoogle Scholar
- Ekengren S, Tryselius Y, Dushay MS, Liu G, Steiner H, Hultmark D: A humoral stress response in Drosophila . Curr Biol 2001, 11: 714-718. 10.1016/S0960-9822(01)00203-2PubMedView ArticleGoogle Scholar
- Agaisse H, Petersen UM, Boutros M, Prevot BM, Perrimon N: Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. Dev Cell 2003, 5: 441-450. 10.1016/S1534-5807(03)00244-2PubMedView ArticleGoogle Scholar
- Agaisse H, Perrimon N: The roles of JAK/STAT signaling in Drosophila immune responses. Immunol Rev 2004, 198: 72-82. 10.1111/j.0105-2896.2004.0133.xPubMedView ArticleGoogle Scholar
- Sabatier L, Jouanguy E, Dostert C, Zachary D, Dimarcq JL, Bulet P, Imler JL: Pherokine-2 and −3. Eur J Biochem 2003, 270: 3398-3407. 10.1046/j.1432-1033.2003.03725.xPubMedView ArticleGoogle Scholar
- Yang WY, Wen SY, Huang YD, Ye MQ, Deng XJ, Han D, Xia QY, Cao Y: Functional divergence of six isoforms of antifungal peptide Drosomycin in Drosophila melanogaster . Gene 2006, 379: 26-32.PubMedView ArticleGoogle Scholar
- Kurata S: Extracellular and intracellular pathogen recognition by Drosophila PGRP-LE and PGRP-LC. Int Immunol 2010, 22: 143-148. 10.1093/intimm/dxp128PubMedPubMed CentralView ArticleGoogle Scholar
- Gregorio ED, Spellman PD, Tzou P, Rubin GM, Lemaitre B: The Toll and Imd pathways are the major regulators of the immune response in Drosophila . EMBO J 2002, 21: 2568-2579. 10.1093/emboj/21.11.2568PubMedPubMed CentralView ArticleGoogle Scholar
- Ragab A, Buechling T, Gesellchen V, Spirohn K, Boettcher AL, Boutros M: Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells. EMBO J 2011, 30: 1123-1136. 10.1038/emboj.2011.4PubMedPubMed CentralView ArticleGoogle Scholar
- Wang XH, Aliyari R, Li WX, Li HW, Kim K, Carthew R, Atkinson P, Ding SW: RNA interference directs innate immunity against viruses in adult Drosophila . Science 2006, 312: 452-454. 10.1126/science.1125694PubMedPubMed CentralView ArticleGoogle Scholar
- Nayak A, Berry B, Tassetto M, Kunitomi M, Acevedo A, Deng C, Krutchinsky A, Gross J, Antoniewski C, Andino R: Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila . Nat Struct Mol Boil 2010, 17: 547-555. 10.1038/nsmb.1810View ArticleGoogle Scholar
- Deddouche S, Matt N, Budd A, Mueller S, Kemp C, Galiana-Arnoux D, Dostert C, Antoniewski C, Hoffmann JA, Imler JL: The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila . Nat Immunol 2008, 9: 1425-1432. 10.1038/ni.1664PubMedView ArticleGoogle Scholar
- Galiana Arnoux D, Dostert C, Schneemann A, Hoffmann JA, Imler JL: Essential function in vivo for Dicer-2 in host defense against RNA viruses in Drosophila . Nat Immunol 2006, 7: 590-597.PubMedView ArticleGoogle Scholar
- Van Rij RP, Saleh MC, Berry B, Foo C, Houk A, Antoniewski C, Andino R: The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster . Genes Dev 2006, 20: 2985-2995. 10.1101/gad.1482006PubMedPubMed CentralView ArticleGoogle Scholar
- Ip YT: Drosophila innate immunity goes viral. Nat Immunol 2005, 6: 863-864. 10.1038/ni0905-863PubMedView ArticleGoogle Scholar
- Stuart LM, Ezekowitz RL: Phagocytosis and comparative innate immunity: learing on the fly. Nat Rev Immunol 2008, 8: 131-141. 10.1038/nri2240PubMedView ArticleGoogle Scholar
- Zhu F, Du HH, Miao ZG, Quan HZ, Xu ZR: Protection of Procambarus clarkii against white spot syndrome virus using inactivated WSSV. Fish Shellfish Immunol 2009, 26: 685-690. 10.1016/j.fsi.2009.02.022PubMedView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.