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
Autor(es): Priya Raj, Dhanwani R, Patro I K, Rao P V L, Parida M M
Resumo: 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 Isl-s, India - 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 - very little is known about the host-pathogen interactions. In the present study replication kinetics - innate immune response of ECSA genotype of CHIKV with - 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-?, OAS-3, MX-2, ISG-15 - Toll like receptors 3 - 7 as compared to non mutant strain (A226). Further pretreatment of N2a cells either with Poly I: C, IFN-? or TNF-? resulted in inhibition of CHIKV replication hence confirming the role of TLR mediated innate immune response in CHIKV pathogenesis. Differential regulation of TLRs - associated down stream antiviral genes might have attributed for increased pathogenesis of the 226V mutant novel ECSA genotype of CHIKV during the recent epidemics.
Palavras-Chave: Antiviral; Chikungunya; N2a cells; Neuropathogenesis; TLR
Imprenta: Infection, genetics and evolution, v. 20, p. 396-406, 2013
Identificador do objeto digital: 10.1016/j.meegid.2013.09.030
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2013
