# The C1QTNF6–MX2 Antiviral Axis Inhibits Porcine Circovirus Type 2 Replication in Porcine Macrophages

## TL;DR

This study shows that C1QTNF6 and MX2 work together to stop PCV2 virus replication in pig cells, offering new ways to fight the disease.

## Contribution

The study identifies a novel C1QTNF6–MX2 antiviral axis that inhibits PCV2 replication in porcine macrophages.

## Key findings

- C1QTNF6 inhibits PCV2 replication by activating interferon-stimulated genes (ISGs) like MX2 and ISG15.
- MX2 overexpression significantly suppresses PCV2 replication, confirming its antiviral role.
- PCV2 infection reduces C1QTNF6, MX2, and IFIT2 expression, impairing antiviral immune responses.

## Abstract

Porcine circovirus type 2 (PCV2), the primary causative agent of postweaning multisystemic wasting syndrome, inflicts substantial economic losses on the global swine industry. C1QTNF6 has emerged as a novel immunoregulatory factor attracting significant interest due to its dual functionality in mediating both pro-inflammatory and antiviral immune responses. In the study, we focused on the C1QTNF6 on PCV2 infection in porcine alveolar macrophages (3D4/21). We found that C1QTNF6 could inhibit PCV2 replication by activating ISGs. Our study provides important insights into PCV2-host interactions and the development of novel antiviral strategies.

Porcine circovirus type 2 (PCV2), a widely distributed immunosuppressive virus, causes substantial economic losses in the global swine industry. C1QTNF6 has emerged as a novel immunoregulatory factor attracting increasing research interest due to its dual roles in both pro-inflammatory and antiviral immune responses. However, the role of C1QTNF6 in regulating PCV2 replication remains poorly characterized. Here, we analyzed C1QTNF6 expression patterns and identified its highly specific expression in placental tissues in both humans and pigs. We then overexpressed C1QTNF6 and conducted RNA sequencing analysis. Remarkably, 68 upregulated genes were identified, and most of them were interferon-stimulated genes (ISGs), including MX2 and ISG15. Functional enrichment analysis revealed that these genes were primarily associated with defense response to viruses and antiviral innate immune response. Subsequently, experimental data show that PCV2 infection significantly suppressed inflammatory responses and markedly downregulated the expression of C1qtnf6, MX2, and IFIT2. Moreover, experimental data indicated that C1QTNF6 inhibits PCV2 replication by targeting ISGs, while restoring MX2 expression. To verify whether C1QTNF6-MX2 antiviral axis mediates this antiviral effect, we constructed an MX2 overexpression plasmid and demonstrated that MX2 overexpression indeed significantly suppressed PCV2 replication. Together, these results provide important insights into PCV2-host interactions and the development of novel antiviral strategies.