show Abstracthide AbstractPorcine circovirus type 2 (PCV2) can cause severe disease in the affected pigs, resulting in massive economic loss for the swine industry. Transcriptomics and proteomics approaches have been widely employed to identify the underlying molecular mechanisms of PCV2 infection. Numerous differentially expressed mRNAs, miRNAs, and proteins, together with their associated signaling pathways, have been identified, paving the way to further validation of their biological functions. Long non-coding RNA (lncRNA) is an important regulator of multiple biological processes. However, rare information regarding its role in the PCV2 infection has been obtained. Hence, in our study, RNA-seq was performed by infecting PK-15 cells with PCV2. Analysis of the differentially expressed genes (DEGs) suggested that cytoskeleton, apoptosis, cell division, and protein phosphorylation were significantly disturbed. Then, using stringent parameters, six lncRNAs were identified. Additionally, the potential targets of the lncRNAs were predicted using both cis- and trans-prediction methods. Interestingly, we found that the HOXB (Homeobox B) gene cluster was probably the target of the lncRNA LOC106505099. Enrichment analysis of the target genes showed that numerous developmental processes were altered during PCV2 infection. Therefore, our study revealed that lncRNAs could affect porcine embryo development through the regulation of the HOXB genes. Overall design: PK-15 cells were cultured in DMEM (Hyclone) with 10% FBS (Hyclone) in 6-well plates until reaching 80% confluency. Then, 3 wells of one plate were infected with Porcine Circovirus type 2 (PCV2) with MOI of 0.1. After 72 hours, the cells were harvested (3 PCV2-infection, 3 for mock infection) were harvested, subjected to total RNA extraction, and sequencing.