Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

• DOI: 10.1128/mbio.02449-17
• Publication Date: 2018-03-05T13:18:03Z
• Authors: Rose M. Langsjoen; Sherry L. Haller; Chad J. Roy; Heather Vinet-Oli...; Nicholas A. Bergren; Jesse H. Erasmus; Jill A. Livengood; Tim D. Powell; Scott C. Weaver; Shannan L. Rossi
• Keywords: Lineage (genetic)

ABSTRACT Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, South (ECSA); Indian Ocean (IOL); Asian. Additionally, the (IOL) sublineage emerged within ECSA clade Asian/American Asian clade. While differences in epidemiological pathological characteristics among involving different lineages sublineages have been suggested, few targeted investigations comparing lineage virulence levels reported. We compared isolates representing all type I interferon receptor-knockout A129 mouse model found lineage-specific virulence. also evaluated cross-protective efficacy IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against isolate YO123223 both murine nonhuman primate models, as well WA SH2830 model. The CHIKV/IRES provided protection mice cohorts Caribbean challenge protected challenge. Taken together, our data suggest that strains are less virulent than those Asian, ECSA, despite virulence, IOL-based offer robust cross-protection from other lineages. Further research needed to elucidate genetic basis for variation corroborate this with human pathogenicity. IMPORTANCE pathogen debilitating disfiguring which last months years after initial fever has resolved. There four CHIKV, two recently sublineages, none Moreover, ability chikungunya vaccines cross-protect heterologous not explored. Therefore, we sought compare lineages, evaluate candidate, models infection. Our results that, although significant were observed elicits cross-lineage protective immunity. These findings provide valuable information predicting severity CHIKV-associated future outbreaks, development considerations.