The research team used MDCC-MSB1 cells, a lymphoblastoid cell line transformed by Marek’s disease virus, as their infection model. This choice matters because CIAV is notoriously difficult to propagate efficiently in standard culture systems, and lymphoblastoid lines provide a permissive environment that approximates the immune cells the virus targets in living birds. By sequencing the full transcriptome of infected versus uninfected cultures, the investigators could detect expression shifts across all four major RNA classes simultaneously rather than examining each in isolation, an approach that reveals regulatory relationships that single-platform studies miss.

The scale of the transcriptional disruption was striking. In total, the team identified 2,590 differentially expressed genes, of which 526 were upregulated and 2,064 were downregulated. The overwhelming bias toward suppression suggests that CIAV infection broadly dampens host gene activity, a pattern consistent with the immunosuppressive character of the disease it causes. Within this total, 539 were protein-coding mRNAs, with 166 increased and 373 decreased in abundance, while the non-coding compartment dominated the response: 1,957 long non-coding RNAs changed expression, 295 up and 1,662 down, alongside 38 microRNAs and 56 circular RNAs.

That lncRNAs account for the majority of altered transcripts is one of the study’s most notable findings. Long non-coding RNAs regulate gene expression at transcriptional, post-transcriptional, and epigenetic levels, and their wholesale suppression during infection hints that CIAV may exploit or disrupt these regulatory layers to reprogram the host cell environment. Because lncRNAs often act in cis near the genes they control or in trans across the genome, their coordinated downregulation could amplify the effects of the mRNA changes observed in the same dataset.

Functional enrichment analysis of the differentially expressed genes pointed to several biological themes. Apoptosis, or programmed cell death, featured prominently, which aligns with the known capacity of CIAV to trigger apoptotic depletion of thymocytes and hematopoietic precursors in infected birds. Transcriptional regulation and phosphorylation-related processes were also enriched, indicating that the virus perturbs the cell’s control circuits at multiple levels. Immune signaling pathways emerged as major hubs, with the p53 tumor-suppressor pathway, the MAPK cascade, and the mTOR pathway all showing significant involvement, linking the viral infection to central nodes that govern cell survival, proliferation, and stress responses.

To move from correlation to candidate regulators, the authors validated a panel of key differentially expressed molecules by quantitative real-time PCR. The validated set included gga-miR-1306-5p, a chicken microRNA whose altered abundance may influence target mRNAs in immune pathways; ARHGEF12, a Rho guanine nucleotide exchange factor that connects extracellular signals to cytoskeletal and transcriptional responses; and three circular RNAs, circMCTP2 derived from the MCTP2 gene, circMAP3K5 derived from MAP3K5, and circPTEN derived from PTEN. Two additional coding genes, ODF1 and ZP2, were also confirmed, expanding the catalog of infection-responsive transcripts beyond the expected immune repertoire.

The circular RNA findings deserve particular attention. CircMAP3K5 and circPTEN are especially intriguing because their linear host genes sit squarely within the MAPK and PI3K-AKT signaling axes that the enrichment analysis flagged. Circular RNAs frequently function as microRNA sponges or protein scaffolds, and changes in their abundance during CIAV infection suggest a layer of post-transcriptional regulation that has been almost entirely unexplored in this viral system. The convergence of altered circular RNAs, microRNAs, and mRNAs within the same pathways strengthens the case that these networks are genuine targets of viral manipulation rather than incidental noise.

From the validated candidates, the team prioritized PTEN and ARHGEF12 as putative regulatory genes shaping CIAV pathogenesis. PTEN encodes a phosphatase that antagonizes the PI3K-AKT-mTOR axis, a pathway controlling cell growth, metabolism, and survival, and its circular RNA counterpart was among the validated differentially expressed transcripts. ARHGEF12, meanwhile, participates in Rho-mediated signaling with documented roles in hematopoietic cell behavior. Both genes occupy central positions in the predicted regulatory networks constructed from the transcriptomic data, making them logical entry points for functional follow-up experiments aimed at determining whether modulating their activity alters viral replication or the host cell fate decisions that follow infection.

The broader significance of the study lies in its contribution to controlling a disease that continues to burden poultry production worldwide. Chicken infectious anemia rarely kills through its acute symptoms alone; instead, it predisposes flocks to secondary viral, bacterial, and fungal infections by crippling immune function, which magnifies losses across the industry. Understanding which host pathways the virus subverts provides molecular targets for antiviral strategies and could inform vaccine design, particularly efforts to induce immune responses that block the immunosuppressive phase of infection. The dataset also supplies a reference transcriptomic resource for future comparative studies, including work with field isolates of differing virulence.

As with any cell-culture transcriptomics study, the findings represent a snapshot of one cell type at a defined stage of infection, and the authors note that further functional validation will be needed to confirm the regulatory roles of PTEN and ARHGEF12 in vivo. Nevertheless, by integrating four RNA species into a single coherent picture, the study demonstrates how whole-transcriptome sequencing can illuminate host-virus interactions that gene-by-gene approaches overlook. For a virus whose defining feature is quiet immune sabotage, seeing the full breadth of the host RNA response is an essential step toward anticipating, and eventually interrupting, the molecular conversations that make chicken infectious anemia such a persistent agricultural problem.

Subject of Research: Host transcriptomic responses to chicken infectious anemia virus infection in a chicken lymphoblastoid cell line

Article Title: Whole-transcriptome sequencing profiling reveals putative regulators and molecular insights into CIAV infection in MDCC-MSB1 cells

Article References: Dong, M., Zhao, Y., Shao, R., Zhang, X., & Liu, Y. (2026). Whole-transcriptome sequencing profiling reveals putative regulators and molecular insights into CIAV infection in MDCC-MSB1 cells. BMC Genomics. https://doi.org/10.1186/s12864-026-13366-7

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13366-7

Keywords: chicken infectious anemia virus, CIAV, transcriptomics, RNA sequencing, MDCC-MSB1, non-coding RNAs, circular RNAs, microRNAs, lncRNAs, PTEN, ARHGEF12, poultry immunosuppression