Sikder, Suchandan, Kumar, Manoharan, Field, Matt, Mee, Peter, Loukas, Alex, Helbig, Karla J., and Sarker, Subir (2026) Transcriptional profiling of the Crocodylus porosus liver cell response to Kunjin virus reveal novel insights into the host-virus interface. Microbial Pathogenesis, 218. 108668.

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Abstract

Crocodilians possess a unique and robust immune system, offering a valuable model for studying vertebrate antiviral responses and informing zoonotic disease surveillance and therapeutic discovery. Building on our previous work that characterized crocodilian immune responses to synthetic viral mimics, this study investigates the innate immune dynamics of Crocodylus porosus liver (LV-1) cells infected with the Kunjin2011 virus, a genetically and antigenically related member of the West Nile virus (WNV) complex. A time-course infection assay was conducted up to 192 h post-infection (hpi), combining viral infectivity analysis with transcriptomic profiling. Delayed Kunjin2011 viral replication was confirmed via qRT-PCR, revealing a clear exponential phase after 48 hpi and peaking at 192 hpi. RNA sequencing demonstrated progressive transcriptional reprogramming in LV-1 cells, with early gene expression changes modest but becoming pronounced by 192 hpi. Differential expression analysis identified 1428 upregulated and 1308 downregulated genes, with temporal shifts from early activation to late-stage suppression. Principal component analysis and hierarchical clustering further supported a time-dependent divergence in host transcriptional responses. Notably, CXCL10, a key immune-associated chemokine, exhibited a biphasic expression pattern, with an early peak at 8 hpi, suppression at intermediate time points, and renewed induction from 72 hpi onwards. Together, these results demonstrate that Kunjin2011 infection elicits a dynamic and time-dependent transcriptional response in C. porosus liver cells, characterized by early activation of innate immune pathways followed by extensive transcriptional remodeling during prolonged infection. This study provides new insights into crocodilian host responses to flavivirus infection and establishes a foundation for future investigations of antiviral immunity and host–virus interactions in reptiles.

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