Genomic and evolutionary characterization of Chandipura virus: a cause of the 2024 outbreak in Gujarat, India.

Acute encephalitis syndrome (AES) caused by Chandipura virus (CHPV) is a rapidly progressive and often fatal neurological illness predominantly affecting children in India. However, limited research on CHPV disease progression and viral genomics has hindered a comprehensive understanding of its transmission dynamics and evolutionary behavior. CHPV is endemic in India, with previous outbreaks (2003-2004) reported case fatality rates (CFRs) ranging from 56% to 75%. In the current (2024) outbreak, the CFR declined to 46%, with an overall test-positivity rate of 18.6%, possibly reflecting improvements in supportive care. Despite advances in genomics and sequencing technologies, only a limited number of CHPV genomes are publicly available. To address this gap, we performed whole-genome sequencing of CHPV isolated from a pediatric patient aged 12 years from Patan, Gujarat. Comparative genomic analysis with previously reported Indian strain revealed approximately 293 mutations, including 24 non-synonymous. The estimated evolutionary rate of CHPV was ~1.62 × 10⁻² substitutions/site/year. Furthermore, the selective pressure analysis showed that, despite the virus being under strong purifying (negative) selection, several non-synonymous changes were identified. Nonetheless, as the present analysis is based on the single genome, further sequencing, validation, and broader comparative analysis are required to draw a definitive inference. However, these findings suggest that even under purifying selection pressure, CHPV retains the ability to infect and cause severe disease in children. This highlights the continued need to investigate virus-host interactions, particularly host immune responses, to better understand CHPV pathogenesis and its ability to cause disease in children. IMPORTANCE: Chandipura virus (CHPV) is an etiological agent of acute encephalitis syndrome (AES) in children, characterized by rapid neurological decline; yet the viral and host factors governing its neuropathogenesis and sudden outbreak dynamics remain poorly defined. Despite minimal genomic variation indicative of strong purifying selection, which supports the continued efficacy of existing molecular diagnostics and candidate therapeutics, CHPV re-emerges unpredictably in human populations, as exemplified by the 2024 AES cluster in Gujarat. This outbreak underscores the importance of continuous genomic surveillance to elucidate viral behavior and immune-evasion mechanisms. Moreover, it highlights the utility of both amplicon-based and metagenomic next-generation sequencing approaches for future CHPV detection and comprehensive genome characterization.