title: Differential regulation of TLR mediated innate immune response of mouse neuronal cells following infection with novel ECSA genotype of Chikungunya virus with and without E1:A226V mutation.
abstract: Chikungunya virus (CHIKV) has received global attention due to the series of large-scale outbreaks in different parts of the world including Africa, Indian Ocean Islands, India and South-East Asia. The appearance of many unusual severe manifestations including neurological disorders was reported in post resurgence epidemics with implication of novel East Central South African (ECSA) genotype with E1:A226V mutation. The molecular mechanism of CHIKV neuropathogenesis is not yet understood and very little is known about the host-pathogen interactions. In the present study replication kinetics and innate immune response of ECSA genotype of CHIKV with and without A226V mutation were determined in mouse neuroblastoma cell line (N2a). The 226V mutant strain was more replication competent in N2a cells with a peak titer of 10(8)PFU/ml compared to 10(6)PFU/ml for A226 virus. Besides, the 226V mutant virus showed relatively less induction of antiviral genes i.e. IFN-β, OAS-3, MX-2, ISG-15 and Toll like receptors 3 and 7 as compared to non mutant strain (A226). Further pretreatment of N2a cells either with Poly I: C, IFN-β or TNF-α resulted in inhibition of CHIKV replication hence confirming the role of TLR mediated innate immune response in CHIKV pathogenesis. Differential regulation of TLRs and associated down stream antiviral genes might have attributed for increased pathogenesis of the 226V mutant novel ECSA genotype of CHIKV during the recent epidemics.
authors.affiliation: Division of Virology, Defence Research & Development Establishment, Gwalior 474002, India.
authors.forename: Raj
authors.initials: R
authors.lastname: Priya
authors.forename: R
authors.initials: R
authors.lastname: Dhanwani
authors.forename: I K
authors.initials: IK
authors.lastname: Patro
authors.forename: P V L
authors.initials: PV
authors.lastname: Rao
authors.forename: M M
authors.initials: MM
authors.lastname: Parida
mesh_terms: D018354:Alphavirus Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D016899:Interferon-beta / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009474:Neurons / Q000469:parasitology; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D016899:Interferon-beta; D011070:Poly I-C
keywords: Antiviral; Chikungunya; N2a cells; Neuropathogenesis; TLR