Time-Resolved Transcriptomic Profiling of Chandipura Virus Infection Reveals Dynamic Host Responses and Host-Directed...

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming-particularly involving lipid and sphingolipid metabolism-was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development.