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Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations.

Abstract：

BACKGROUND:Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10-20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components. METHODOLOGY:Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components. Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico. An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides. Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology. FINDINGS:The serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection. Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone. Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone. Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Reddy V,Desai A,Krishna SS,Vasanthapuram R

doi

10.1371/journal.pntd.0005238

subject

Has Abstract

pub_date

2017-01-26 00:00:00

pages

e0005238

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-16-00867

journal_volume

pub_type

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Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations.