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Article

African Swine Fever Virus CD2v Protein Induces β-Interferon Expression and Apoptosis in Swine Peripheral Blood Mononuclear Cells

1
Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA
2
School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Manuel Borca
Received: 1 July 2021 / Revised: 23 July 2021 / Accepted: 25 July 2021 / Published: 28 July 2021
(This article belongs to the Special Issue African Swine Fever Virus 2021)
African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and macrophages with CD2v protein induced apoptosis. Immunoprecipitation and colocalization studies revealed that CD2v interacts with CD58, the natural host CD2 ligand. Additionally, CD58 knockdown in cells or treatment of cells with an NF-κB inhibitor significantly reduced CD2v-mediated NF-κB activation and IFN-β induction. Further, antibodies directed against CD2v inhibited CD2v-induced NF-κB activation and IFN-β transcription in cells. Overall, results indicate that ASFV CD2v activates NF-κB, which induces IFN signaling and apoptosis in swine lymphocytes/macrophages. We propose that CD2v released from infected macrophages may be a significant factor in lymphocyte apoptosis observed in lymphoid tissue during ASFV infection in pigs. View Full-Text
Keywords: African swine fever virus; CD2v; interferon-β; NF-κB; CD58; lymphocyte; macrophage; apoptosis; pathogenesis African swine fever virus; CD2v; interferon-β; NF-κB; CD58; lymphocyte; macrophage; apoptosis; pathogenesis
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MDPI and ACS Style

Chaulagain, S.; Delhon, G.A.; Khatiwada, S.; Rock, D.L. African Swine Fever Virus CD2v Protein Induces β-Interferon Expression and Apoptosis in Swine Peripheral Blood Mononuclear Cells. Viruses 2021, 13, 1480. https://0-doi-org.brum.beds.ac.uk/10.3390/v13081480

AMA Style

Chaulagain S, Delhon GA, Khatiwada S, Rock DL. African Swine Fever Virus CD2v Protein Induces β-Interferon Expression and Apoptosis in Swine Peripheral Blood Mononuclear Cells. Viruses. 2021; 13(8):1480. https://0-doi-org.brum.beds.ac.uk/10.3390/v13081480

Chicago/Turabian Style

Chaulagain, Sabal, Gustavo A. Delhon, Sushil Khatiwada, and Daniel L. Rock 2021. "African Swine Fever Virus CD2v Protein Induces β-Interferon Expression and Apoptosis in Swine Peripheral Blood Mononuclear Cells" Viruses 13, no. 8: 1480. https://0-doi-org.brum.beds.ac.uk/10.3390/v13081480

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