Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway
- 1k Downloads
Newcastle disease virus (NDV) is an avian paramyxovirus that can selectively replicate in and destroy human tumor cells. In this report, we demonstrate that NDV infection in HeLa cells leads to the activation of the pattern recognition Toll-like receptor 3 (TLR3). Overexpression of TLR3 enhanced the activity of the IFN-β promoter and the transcription factor NF-kappa B (NF-κB), thereby decreasing viral protein synthesis and the virus titer. In addition, the reduction of endogenous TLR3 by small interfering RNA (siRNA) increased NDV replication. Similar anti-NDV effects were observed in DF-1 chicken fibroblast cells with the exogenous expression of chicken TLR3 (cTLR3). Immunofluorescence staining of HeLa cells indicated that the dsRNA generated during NDV replication colocalized with TLR3 in punctate subcellular structures. Altogether, our results strongly suggest that TLR3 actively participates in the recognition of the innate pro-inflammatory response after NDV infection and leads to the consequent antiviral cytokine/interferon secretion.
KeywordsRespiratory Syncytial Virus West Nile Virus Newcastle Disease Virus TLR3 Expression Newcastle Disease Virus Strain
We are grateful to Professor Takashi Fujita (Kyoto University, Japan) for providing the p125-luc plasmid. This work was financially supported by the Chinese National High-Tech R&D Program (2011AA10A209), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the China Agriculture Research System (CARS-41-K08), and the Chinese Special Fund for Agro-Scientific Research in the Public Interest (201003012 and 201303033).
- 1.Alexander D (1997) Newcastle disease and other avian Paramyxoviridae infections. In: Caineck BW (ed) Diseases of poultry. Iowa State University Press, Ames, pp 541–569Google Scholar
- 3.Boukhvalova MS, Sotomayor TB, Point RC, Pletneva LM, Prince GA, Blanco JC (2010) Activation of interferon response through toll-like receptor 3 impacts viral pathogenesis and pulmonary toll-like receptor expression during respiratory syncytial virus and influenza infections in the cotton rat Sigmodon hispidus model. J Interferon Cytokine Res: Off J Int Soc Interferon Cytokine Res 30:229–242CrossRefGoogle Scholar
- 11.Jiang Z, Zamanian-Daryoush M, Nie H, Silva AM, Williams BR, Li X (2003) Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR. J Biol Chem 278:16713–16719PubMedCrossRefGoogle Scholar
- 13.Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105Google Scholar
- 14.Lamb RA, Griffin DE (2007) Paramyxoviridae: the viruses and their replication. In: Knipe DM (ed) Field virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1449–1496Google Scholar
- 16.Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, Si-Tahar M (2007) Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol 178:3368–3372Google Scholar
- 26.Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P, Weber F, Reis e Sousa C (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Science 314:997–1001Google Scholar
- 36.Trapp S, Derby NR, Singer R, Shaw A, Williams VG, Turville SG, Bess JW Jr, Lifson JD, Robbiani M (2009) 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 83:884–895PubMedCrossRefPubMedCentralGoogle Scholar