show Abstracthide AbstractEpstein-Barr virus (EBV) infection in humans is ubiquitous and is associated with a spectrum of human diseases. Remodeling the immune microenvironment is the major reason for EBV infection and pathogenesis, but the mechanism has not been fully elucidated. In this study, we used whole-transcriptome RNA-seq to detect mRNAs, long non-coding RNAs (lncRNAs) and microRNAs(miRNAs) profiles in control group, 3 days after EBV infection group and 28 days group after EBV infection based on tree shrew model that we reported previously. Firstly, we estimated the proportion of 22 cell types in each sample using CIBERSORT software and identified 18 high-confidence DELncRNAs which related to immune microenvironment regulation after EBV infection. Functional enrichment analysis of these differentially expressed LncRNAs co-expressed mRNAs mainly focused on the autophagy, endocytosis and ferroptosis signaling pathways. Moreover, EBV infection affects the pattern of miRNA expression and large amounts of miRNAs were silenced. Finally, three ceRNA regulatory network were built by using LncRNAs significantly correlated with immune cell types, miRNAs responded to EBV infection, and potential target mRNA of the miRNAs. Overall, we conducted for the first time a full transcriptomic analysis of EBV infection in vivo, the present study provides a novel perspective for further investigation on EBV-host interactions.