Clinical and Genomic Characterization of Chikungunya Virus Variant reveals a Novel nsP3 H377P Substitution during the 2015 Outbreak in Central Valley of Chiapas, Mexico.

OBJECTIVES: To characterize the clinical, diagnostic and genomic features of chikungunya virus (CHIKV) infection among patients presenting with an acute dengue-like illness in the inland Central Valley of Chiapas, Mexico, during the 2015 outbreak. METHODS: We retrospectively tested sera from 80 suspected cases using qRT-PCR, virus isolation, ELISA, indirect immunofluorescence, full-genome sequencing and phylogenetic analyses compared Central Valley isolates with contemporary CHIKV sequences from Mexico and the Americas. RESULTS: Sixty-seven patients (84%) were CHIKV-positive, including four CHIKV-DENV coinfections and serological evidence of prior DENV exposure in (60%) of cases. Fever and polyarthralgia occurred in all confirmed cases; headache, myalgia, conjunctivitis, rash, lymphadenopathy, and lymphopenia were also frequent. Two full genomes (PQ261036, PQ261037) clustered in the Asian/American lineage but formed a distinct subclade from coastal strains, one isolate carried a novel nsP3 H377P substitution in the hypervariable domain. CONCLUSIONS: CHIKV accounted for a substantial proportion of dengue-like illness during this inland outbreak, underscoring the limits of clinical diagnosis where CHIKV and DENV co-circulate. Genomic data revealed distinguishable Asian CHIKV variants and a previously unreported nsP3 substitution, supporting continued genomic surveillance of CHIKV in southern Mexico.