Study on host-pathogen interactions of Palyam serogroup viruses using a novel immortalized bovine cerebrum cell line

Orbivirus palyamense belongs to the group of arthropod-borne viruses often referred to as Palyam serogroup viruses (PALV), which include Chuzan virus (CHUV), D'Aguilar virus (DAGV), and Bunyip Creek virus (BCV). Several members of this serogroup have been implicated in congenital abnormalities with gross lesions in brain tissues. CHUV causes congenital abnormalities in cattle, whereas other serotypes show variable pathogenicity, with DAGV being sporadically associated with congenital abnormalities and BCV showing no clear disease causality. To elucidate the mechanisms underlying these clinical differences at the cellular level, we established a novel immortalized bovine cerebral-derived cell line (IKBC), as an in vitro model. An RNA sequencing analysis revealed that IKBC cells exhibited neuroepithelial-like properties with the partial expression of immature neuron markers and some mesenchymal-like features consistent with an epithelial-mesenchymal transition-like state. Infection assays demonstrated that CHUV exerted stronger cytopathic effects and tended to replicate more efficiently in IKBC cells than DAGV and BCV. The expression of type I interferon and more downstream interferon-stimulated genes (ISGs) in IKBC cells was more strongly and weakly induced, respectively, by CHUV infection than by DAGV or BCV infection. To assess strain-specific differences, comparisons among CHUV strains revealed that those isolated during large-scale outbreaks more weakly induced the expression of ISGs than strains from sporadic occurrences, suggesting that viral immunosuppressive properties contributed to the magnitude of the epidemics. Overall, IKBC cells provide unique models for investigating the characteristics and pathogenesis of PALV in cattle.