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

Citation: Reddy V, Desai A, Krishna SS, Vasanthapuram R (2017) Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations. PLoS Negl Trop Dis 11(1): e0005238. doi:10.1371/journal.pntd.0005238
Published: January 26, 2017

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.

Author Summary: The outcome of Chikungunya virus infection is usually benign but persistent arthritis has been reported in 10–20% of patients after Chikungunya fever. However, some reports have suggested that similarity between host proteins and viral proteins (molecular mimicry) leads to immune mediated damage. However, this has not been proved conclusively. Therefore, this study was undertaken to identify if molecular mimicry exists between CHIKV and host components. Using various bioinformatics tools we identified common sequences and structural homology between glycoprotein of the virus and two human host tissue proteins- HLA-B27 molecule and a domain of complement C3. Two peptides having homology to these human tissue components were synthesized. These peptides were recognized by antibodies present in serum of CHIKV patients. Experiments were conducted to investigate if the peptides were capable of inducing pathology in an experimental C57BL/6J mouse model. Both the peptides on their own 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 injected initially with CHIKV followed by a subsequent injection of the two CHIKV peptides exhibited increased pathology as compared to animals that were injected with peptides or virus alone.

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