AUTHOR=Jiang Yitong , Jiang Fei , Zhai Wenzhu , Huang Ying , Pang Zhongbao , Tao Chunhao , Wang Zhen , He Yuheng , Chu Yuanyuan , Zhu Hongfei , Wu Jiajun , Jia Hong 

TITLE=Swine IFN cocktail can reduce mortality and lessen the tissue injury caused by African swine-fever-virus-infected piglets

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1388035

DOI=10.3389/fcimb.2024.1388035

ISSN=2235-2988

ABSTRACT=<p>African swine fever (ASF), a highly virulent viral infection, poses a significant threat to the global pig industry. Currently, there are no commercially available vaccines against ASF. While the crucial role of interferon (IFN) in combating viral infections is well-established, its impact on the clinical signs and mortality rates of ASF remains unclear. In this study, swine IFN-α2, IFN-γ, and IFN-λ3 were fused with the Fc segment of immunoglobulin G (IgG) and expressed in mammalian cells (293T), and the antiviral efficacy were detected by VSV-3D4/2 and VSV-PK15 systems. Then, the interferon stimulating genes (ISGs) induced by IFNs-hFc in 3D4/2 cells were determined by qRT-PCR. Also, the preventive potential of the interferon (IFN) cocktail (a mixture of IFNα2-hFc, IFNγ-hFc, and IFNλ3-hFc) were evaluated <italic>in vivo</italic> by 25-day-old piglets. The results showed that the specific activities of IFNα2-hFc, IFNγ-hFc, and IFNλ3-hFc were 2.46 × 10<sup>7</sup> IU/mL, 4.54 × 10<sup>9</sup> IU/mL and 7.54 × 10<sup>10</sup> IU/mL, respectively. The IFN-hFc significantly induced the expression of various IFN-stimulated genes (ISGs) in 3D4/2 cells after IFNs-Fc treatment, including <italic>IFIT5</italic>, <italic>Mx1</italic>, <italic>OASL</italic>, <italic>ISG12</italic>, <italic>STAT1</italic>, <italic>IRF1</italic>, <italic>PKR</italic>, <italic>CXCL10</italic>, and <italic>GBP1</italic>. Furthermore, the IFN cocktail treatment reduced the viral load, delayed death, and reduced tissue injury in the piglets infected with ASF virus (ASFV). in conclusion, these results suggest that the IFNs-hFc showed high anti-viral activity, and the IFN cocktail may be potential for the prevention and treatment of ASF.</p>