Unravelling the genomic epidemiology and antigenic evolution of Chandipura virus: A genetically constrained neurotropic threat

Abstract

Spanning almost six decades (1966–2024), 23 whole-genome sequences of Chandipura virus (CHPV), a neurotropic rhabdovirus associated with acute encephalitis primarily in India, have been analyzed. The virus is believed to be transmitted mainly by Sergentomyia and Phlebotomus sandflies. An epidemiological geographical map was developed showing global CHPV detection in sandflies, district-level human encephalitis reports in India, and sandfly species distribution across the country. This integrated landscape links viral occurrence with vector ecology and outbreak potential. To investigate evolutionary dynamics, we analyzed 23 complete genomes, comprising 5 human-derived isolates from India, 17 sandfly-derived isolates from Senegal and Kenya, and one hedgehog-derived isolate from Nigeria. Phylogenetic reconstruction revealed clear lineage segregation between Indian and African strains, indicating region-specific evolution. Despite this divergence, overall genomic variability remained low. Among all genes, the phosphoprotein exhibited relatively higher variability, while human-derived Indian sequences showed lower genetic diversity than the predominantly sandfly-derived African sequences; however, this comparison is confounded by differences in geography, sampling period, and host origin. Selection pressure analyses indicated predominantly purifying selection across coding regions. Episodic diversification analysis detected adaptive events in structural proteins. In the glycoprotein, all diversification sites (P272H, L424W, K503R) overlapped with predicted B-cell epitopes. In the matrix protein, both sites (K20R, D97N) mapped to predicted B-cell epitope regions. In contrast, among the two diversification sites in the nucleoprotein (N35E, A187V), only A187V overlapped with an epitope, whereas N35E was outside predicted antigenic domains. Collectively, these findings provide a comprehensive evolutionary and epidemiological perspective on CHPV and highlight the urgent need for systematic genomic surveillance to inform future diagnostic, vaccine and public health intervention strategies.