Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

Virology Journal

Surapee Anantapreecha¹  Naokazu Takeda²  Kazuyoshi Ikuta³  Takeshi Kurosu³  Masanori Kameoka²  Yang Pan³  Atchareeya A-nuegoonpipat¹  Nitchakarn Noranate²  Uranan Tumkosit²  Uamporn Siripanyaphinyo²  Yong-Gang Li³ 

[1] National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand;Section of Viral Infections, Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections, Nonthaburi, 11000, Thailand;Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

关键词: TLR3;    BEAS-2B cells;    Poly (I:C);    Chikungunya virus;   

Others  :  1154499
DOI  :  10.1186/1743-422X-9-114

 received in 2011-06-24, accepted in 2012-06-01,  发布年份 2012

【 摘 要 】

Background

Double-stranded RNA (dsRNA) and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C)], are recognized by toll-like receptor 3 (TLR3) and induce interferon (IFN)-β in many cell types. Poly (I:C) is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C) elicited IFN-α/β production and natural killer (NK) cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV) infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance.

Results

The effects of Poly (I:C) on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C)-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C) treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells.

Conclusions

CHIKV is sensitive to innate immune response induced by Poly (I:C). The inhibition of CHIKV replication by Poly (I:C) may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

【 授权许可】

   
2012 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Lumsden WH: An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. II. General description and epidemiology. Trans R Soc Trop Med Hyg 1955, 49:33-57.
• [2]Robinson MC: An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. I. Clinical features. Trans R Soc Trop Med Hyg 1955, 49:28-32.
• [3]McIntosh B M JPGaDSI: Rural epidemic of Chikungunya in South Africa with involvement of aedes (Diceromyia) furcifer (Edwards) and baboons:S. Afr: J Sci 1977, 73:267-269.
• [4]Burke CW, Gardner CL, Steffan JJ, Ryman KD, Klimstra WB: Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses. Virology 2009, 395:121-132.
• [5]Lam SK, Chua KB, Hooi PS, Rahimah MA, Kumari S, Tharmaratnam M, Chuah SK, Smith DW, Sampson IA: Chikungunya infection–an emerging disease in Malaysia. Southeast Asian J Trop Med Public Health 2001, 32:447-451.
• [6]Munasinghe DR, Amarasekera PJ, Fernando CF: An epidemic of dengue-like fever in Ceylon (chikungunya–a clinical and haematological study. Ceylon Med J 1966, 11:129-142.
• [7]Pavri K: Disappearance of Chikungunya virus from India and South East Asia. Trans R Soc Trop Med Hyg 1986, 80:491.
• [8]Chastel C: Chikungunya virus: its recent spread to the southern Indian Ocean and Reunion Island (2005–2006). Bull Acad Natl Med 2005, 189:1827-1835.
• [9]Enserink M: Infectious diseases. Massive outbreak draws fresh attention to little-known virus. Science 2006, 311:1085.
• [10]Higgs S: The 2005–2006 Chikungunya epidemic in the Indian Ocean. Vector Borne Zoonotic Dis 2006, 6:115-116.
• [11]Ligon BL: Reemergence of an unusual disease: the chikungunya epidemic. Semin Pediatr Infect Dis 2006, 17:99-104.
• [12]Paganin F, Borgherini G, Staikowsky F, Arvin-Berod C, Poubeau P: Chikungunya on Reunion Island: chronicle of an epidemic foretold. Presse Med 2006, 35:641-646.
• [13]Robinson MC: An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. I. Clinical features. Trnas R Soc Trop Med Hyg 1955, 49:28-32.
• [14]Lumsden WH: An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. II. General description and epidemiology. Tran R Soc Trop Med Hyg 1955, 49:33-57.
• [15]Pongsiri P, Auksornkitti V, Theamboonlers A, Luplertlop N, Rianthavorn P, Poovorawan Y: Entire genome characterization of Chikungunya virus from the 2008–2009 outbreaks in Thailand. Trop Biomed 2010, 27:167-176.
• [16]Charrel RN, de Lamballerie X, Raoult D: Chikungunya outbreaks–the globalization of vectorborne diseases. N Engl J Med 2007, 356:769-771.
• [17]Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, Cordioli P, Fortuna C, Boros S, Magurano F, et al.: Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007, 370:1840-1846.
• [18]Chevillon C, Briant L, Renaud F, Devaux C: The Chikungunya threat: an ecological and evolutionary perspective. Trends Microbiol 2008, 16:80-88.
• [19]Mavalankar D, Shastri P, Bandyopadhyay T, Parmar J, Ramani KV: Increased mortality rate associated with chikungunya epidemic, Ahmedabad, India. Emerg Infect Dis 2008, 14:412-415.
• [20]Laurent P, Le Roux K, Grivard P, Bertil G, Naze F, Picard M, Staikowsky F, Barau G, Schuffenecker I, Michault A: Development of a sensitive real-time reverse transcriptase PCR assay with an internal control to detect and quantify chikungunya virus. Clin Chem 2007, 53:1408-1414.
• [21]Carey DE, Myers RM, DeRanitz CM, Jadhav M, Reuben R: The 1964 chikungunya epidemic at Vellore, South India, including observations on concurrent dengue. Trans R Soc Trop Med Hyg 1969, 63:434-445.
• [22]Brighton SW, Prozesky OW, de la Harpe AL: Chikungunya virus infection. A retrospective study of 107 cases. S Afr Med J 1983, 63:313-315.
• [23]Schwartz O, Albert ML: Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol 2010, 8:491-500.
• [24]Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F, Rudnicka D, Sol-Foulon N, Le Roux K, Prevost MC, Fsihi H, et al.: Characterization of reemerging chikungunya virus. PLoS Pathog 2007, 3:e89.
• [25]Couderc T, Chretien F, Schilte C, Disson O, Brigitte M, Guivel-Benhassine F, Touret Y, Barau G, Cayet N, Schuffenecker I, et al.: A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog 2008, 4:e29.
• [26]Jacobs BL, Langland JO: When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology 1996, 219:339-349.
• [27]Field AK, Tytell AA, Lampson GP, Hilleman MR: Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. Proc Natl Acad Sci U S A 1967, 58:100-1010.
• [28]Djeu JY, Heinbaugh JA, Holden HT, Herberman RB: Role of macrophages in the augementation of mouse natural killer cell activity by poly I:C and interferon. J Immunol 1979, 122:182-188.
• [29]Gidlund M, Orn A, Wigzell H, Senik A, Gresser I: Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 1978, 273:759-761.
• [30]Matsumoto M, Seya T: TLR3: interferon induction by double-stranded RNA including poly(I:C). Adv Drug Deliv Rev 2008, 60:805-812.
• [31]Guillot L, Le Goffic R, Bloch S, Escriou N, Akira S, Chignard M, Si-Tahar M: Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 2005, 280:5571-5580.
• [32]Rudd BD, Burstein E, Duckett CS, Li X, Lukacs NW: Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. J Virol 2005, 79:3350-3357.
• [33]Ashkar AA, Yao XD, Gill N, Sajic D, Patrick AJ, Rosenthal KL: Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA. J Infect Dis 2004, 190:1841-1849.
• [34]Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, et al.: Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 2004, 101:3516-3521.
• [35]Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B, Flavell RA, Diamond MS, Colonna M: Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci U S A 2006, 103:8459-8464.
• [36]Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T: The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004, 5:730-737.
• [37]Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, et al.: Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005, 175:2851-2858.
• [38]Alexopoulou L, Holt AC, Medzhitov R, Flavell RA: Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001, 413:732-738.
• [39]Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T: Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem Biophys Res Commun 2002, 293:1364-1369.
• [40]Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S: Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 2003, 301:640-643.
• [41]Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T: TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003, 4:161-167.
• [42]Samuel CE: Antiviral actions of interferons. Clin Microbiol Rev 2001, 14:778-809. table of contents
• [43]Takeuchi O, Hemmi H, Akira S: Interferon response induced by Toll-like receptor signaling. J Endotoxin Res 2004, 10:252-256.
• [44]Le Bon A, Tough DF: Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 2002, 14:432-436.
• [45]Koyama S, Ishii KJ, Coban C, Akira S: Innate immune response to viral infection. Cytokine 2008, 43:336-341.
• [46]Sen GC, Sarkar SN: Transcriptional signaling by double-stranded RNA: role of TLR3. Cytokine Growth Factor Rev 2005, 16:1-14.
• [47]Juang YT, Lowther W, Kellum M, Au WC, Lin R, Hiscott J, Pitha PM: Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc Natl Acad Sci U S A 1998, 95:9837-9842.
• [48]Lin R, Heylbroeck C, Pitha PM, Hiscott J: Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol Cell Biol 1998, 18:2986-2996.
• [49]Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T: Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell 1998, 1:507-518.
• [50]Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T: Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J 1998, 17:1087-1095.
• [51]Kumar A, Zhang J, Yu FS: Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells. Immunology 2006, 117:11-21.
• [52]Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M: Toll-like receptor 3 ligand-induced antiviral response in mouse osteoblastic cells. Int J Mol Med 2007, 19:771-775.
• [53]Abrahams VM, Schaefer TM, Fahey JV, Visintin I, Wright JA, Aldo PB, Romero R, Wira CR, Mor G: Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I:C). Hum Reprod 2006, 21:2432-2439.
• [54]Chelbi-Alix MK, Belforte B, Saal F, Lasneret J, Peries J, Thang MN: The effects of poly(I).poly(C12U) and interferon on the multiplication of a mammalian type C retrovirus in human cells. J Gen Virol 1992, 73(Pt 9):2291-2297.
• [55]Trapp S, Derby NR, Singer R, Shaw A, Williams VG, Turville SG, Bess JW, Lifson JD, Robbiani M: Double-stranded RNA analog poly(I:C) inhibits human immunodeficiency virus amplification in dendritic cells via type I interferon-mediated activation of APOBEC3G. J Virol 2009, 83:884-895.
• [56]Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S: Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 2002, 169:6668-6672.
• [57]Li K, Chen Z, Kato N, Gale M, Lemon SM: Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. J Biol Chem 2005, 280:16739-16747.
• [58]Schilte C, Couderc T, Chretien F, Sourisseau M, Gangneux N, Guivel-Benhassine F, Kraxner A, Tschopp J, Higgs S, Michault A, et al.: Type I IFN controls chikungunya virus via its action on nonhematopoietic cells. J Exp Med 2009, 207:429-442.
• [59]Ichinohe T, Watanabe I, Ito S, Fujii H, Moriyama M, Tamura S, Takahashi H, Sawa H, Chiba J, Kurata T, et al.: Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection. J Virol 2005, 79:2910-2919.
• [60]Ichinohe T, Watanabe I, Tao E, Ito S, Kawaguchi A, Tamura S, Takahashi H, Sawa H, Moriyama M, Chiba J, et al.: Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvant. J Med Virol 2006, 78:954-963.
• [61]Ichinohe T, Ainai A, Tashiro M, Sata T, Hasegawa H: PolyI:polyC12U adjuvant-combined intranasal vaccine protects mice against highly pathogenic H5N1 influenza virus variants. Vaccine 2009, 27:6276-6279.
• [62]Stahl-Hennig C, Eisenblatter M, Jasny E, Rzehak T, Tenner-Racz K, Trumpfheller C, Salazar AM, Uberla K, Nieto K, Kleinschmidt J, et al.: Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog 2009, 5:e1000373.