Neglected spleen transcriptional profile reveals disturbed host inflammatory response to Rabbit hemorrhagic disease virus 2 infection in adult rabbits

Abstract: Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the lagovirus rabbit hemorrhagic disease virus (RHDV). In April 2020, type 2 RHDV (RHDV2/b/GI.2) emerged in China, then caused great economic losses to rabbit raising industry in our country. Here a formerly isolated RHDV2 strain, referred to RHDV2-CHN/SC2020 from domestic rabbit farms experiencing RHD outbreaks in Sichuan province. To better understand the pathogenic mechanisms after RHDV2 infection, we compared transcriptomic changes of spleen and evaluated the differential expression of genes by RNA-Seq and real-time qPCR. Our data suggested that rabbit adults infected with RHDV2 had constitutively heightened inflammatory responses compared to the control group, with 3148 differentially expressed genes (DEGs) was identified. These DEGs were associated with disease, signal transduction, cellular process and cytokine signaling categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly significantly enriched in pathways such as cytokine-cytokine receptor interaction signaling pathway, which might play a vital role in CHN/SC2020 infection. Meanwhile proinflammatory cytokines and chemokines were significantly increased in spleen at the late infection stage. The result indicated that infection with RHDV2-CHN/SC2020 could activate inflammatory pathways in spleen, and possibly trigger largescale cytokine production. Our analysis provides useful initial data towards better understanding of the pathogenic mechanism of RHDV2.