ABSTRACT: Chicken infectious anaemia (CIA) is an immunosuppressive disease caused by chicken infectious anaemia virus (CIAV). Due to immunosuppression, the disease is often leads to mixed infections and secondary infections, exacerbating viral, bacterial, and fungal infections, which can be highly detrimental. Therefore, it is imperative to identify the immune genes involved in regulating CIAV infection. In this study, comprehensive transcriptome sequencing was employed to determine the expression levels of regulated immune genes including mRNAs, microRNAs, lncRNAs, and circRNAs in CIAV-infected MDCC-MSB1 cells. A total of 2590 differentially expressed genes were identified in CIAV-infected MDCC-MSB1 cells, of which 526 were up-regulated. There were 539 differentially expressed mRNAs, including 166 up-regulated mRNAs, 38 differentially expressed microRNAs, including 22 up-regulated microRNAs, 1957 differentially expressed lncRNAs, including 295 up-regulated lncRNAs, and 56 differentially expressed circRNAs, including 43 up-regulated circRNAs. Subsequently, we selected the top 20 significantly up-regulated differentially expressed genes (GEM, ODF1, ARHGEF12, DOC2B, ZP2, gga-miR-1306-5p_L-1R-2, gga-miR-6615-3p, gga-mir-3535-p5, gga-miR-726-5p_1ss4AG, gga-miR-458a-3p, ENSGALG00010010181, ENSGALG00010002366, ENSGALG00010019353, ENSGALG00010029120, ENSGALG00010026718, circMAP3K5, ENSGALG00010015867, circGALNT1, circMCTP2, circPTEN) among the 526 up-regulated differentially expressed genes for Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and we found that those 20 genes were significantly enriched in key pathways such as apoptosis, transcriptional regulation, MAPK signaling pathway, p53 signaling pathway and phosphatidylinositol signaling system. qRT-PCR was used to further verify the accuracy of RNA sequencing at the transcriptional level. In summary, this study provides a theoretical foundation for future prevention and control strategies against CIAV, while further investigation is required to elucidate the functions and mechanisms underlying these significantly differentially expressed genes.