Joydeep, Nag and Reshma, Reshma K M and Suma, S M and Umerali , Kunnakkadan and Nisha , Asok Kumar and John , Bernet Johnson (2020) A Factor I-Like Activity Associated with Chikungunya VirusContributes to Its Resistance to the Human ComplementSystem. Journal of Virology, 94 (7). ISSN 0022-538X

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Abstract

Chikungunya virus (CHIKV) is an emerging pathogen capable of causingexplosive outbreaks. Prior studies showed that exacerbation in arthritogenic alpha-virus-induced pathogenesis is attributed to its interaction with multiple immunecomponents, including the complement system. Viremia concomitant to CHIKV in-fection makes exposure of the virus to complement unavoidable, yet very little isknown about CHIKV-complement interactions. Here, we show that CHIKV activatedserum complement to modest levels in a concentration- and time-dependent man-ner, but the virus effectively resisted complement-mediated neutralization. Heat-inactivated serum from seropositive donors could actively neutralize CHIKV due tothe presence of potent anti-CHIKV antibodies. Deposition of key complement com-ponents C3 and C4 did not alter the resistance of CHIKV to complement. Further, weidentified a factor I-like activity in CHIKV that limited complement by inactivatingC3b into inactive C3b (iC3b), the complement component known to significantlycontribute to disease severityin vivo, but this activity had no effect on C4b. Inactiva-tion of C3b by CHIKV was largely dependent on the concentration of the solublehost cofactor factor H and the virus concentration. A factor I function-blocking anti-body had only a negligible effect on the factor I-like activity associated with CHIKV,suggesting that this activity is independent of host factor I and could be of viral ori-gin. Thus, our findings suggest a complement modulatory action of CHIKV whichnot only helps the virus to evade human complement but may also have implica-tions in alphavirus-induced arthritogenic symptoms.IMPORTANCEChikungunya virus is a vector-borne pathogen of global significance.The morbidity associated with chikungunya virus (CHIKV) infection, neurovirulenceand adaptability toAedes albopictus, necessitates a deeper understanding of the in-teraction of CHIKV with the host immune system. Here, we demonstrate that CHIKVis resistant to neutralization by one of the potent barriers of the innate immunearm, the complement system. Chikungunya virus showed marked resistance to com-plement despite activation and deposition of complement proteins. Interestingly theC3 component associated with the virion was found to be inactive C3b (iC3b), a keyfactor implicated in the pathogenesis and disease severity in the mouse model ofRoss River virus infection. CHIKV also had an associated unique factor I-like activitythat mediated the inactivation of C3b into iC3b. We have unraveled a smart strategyadopted by CHIKV to limit complement which has serious implications in viral dis-semination, pathogenesis, and disease.

Item Type:	Article
Uncontrolled Keywords:	chikungunya virus, complement activation, complement evasion, factorI-like activity
Subjects:	Viral Disease Biology
Depositing User:	Central Library RGCB
Date Deposited:	08 Jan 2021 07:02
Last Modified:	08 Jan 2021 07:02
URI:	http://rgcb.sciencecentral.in/id/eprint/1000

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