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

Raj Priya, R. Dhanwani, I. K. Patro, P. V L Rao, M. M. Parida

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 108PFU/ml compared to 106PFU/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.

Original languageEnglish (US)
Pages (from-to)396-406
Number of pages11
JournalInfection, Genetics and Evolution
Volume20
DOIs
StatePublished - Jan 1 2013

Fingerprint

Chikungunya virus
immune response
Innate Immunity
mutation
virus
genotype
neurons
Genotype
Mutation
mice
Infection
infection
mutants
Antiviral Agents
pathogenesis
Indian Ocean Islands
Toll-Like Receptor 7
Toll-Like Receptor 3
Viruses
Host-Pathogen Interactions

Keywords

  • Antiviral
  • Chikungunya
  • N2a cells
  • Neuropathogenesis
  • TLR

Cite this

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. / Priya, Raj; Dhanwani, R.; Patro, I. K.; Rao, P. V L; Parida, M. M.

In: Infection, Genetics and Evolution, Vol. 20, 01.01.2013, p. 396-406.

Research output: Contribution to journalArticle

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