Exploring Virus–Host Interactions Through Combined Proteomic Approaches Identifies BANF1 as a New Essential Factor for African Swine Fever Virus

作者：Juliette Dupré, Katarzyna Magdalena Dolata, Gang Pei, Aidin Molouki, Lynnette C. Goatley, Richard Küchler, Timothy K. Soh, Jens B. Bosse, Aurore Fablet, Mireille Le Dimna, Grégory Karadjian, Edouard Hirchaud, Christopher L. Netherton, Linda K. Dixon, Ana Luísa Reis, Damien Vitour, Marie‐Frédérique Le Potier, Axel Karger, Grégory Caignard · 发表于：Molecular & Cellular Proteomics · 年份：2025 · DOI：10.1016/j.mcpro.2025.101038 · 被引用次数：2 · 研究领域：Animal Disease Management and Epidemiology、Virus-based gene therapy research、Animal Virus Infections Studies

African swine fever virus (ASFV) causes a lethal disease in pigs and represents a significant threat to the global pork industry due to the lack of effective vaccines or treatments. Despite intensive research, many ASFV proteins remain uncharacterized. This study aimed to elucidate the functions of two ASFV proteins, pMGF360-21R and pA151R, through comprehensive analysis of their interactions with host proteins. Using affinity purification-mass spectrometry and yeast two-hybrid screening approaches, we identified the host protein barrier-to-autointegration factor 1 (BANF1) as a key interactor of both viral proteins. Biochemical and colocalization assays confirmed these interactions and demonstrated that MGF360-21R and A151R expression leads to cytoplasmic relocation of BANF1. Functionally, BANF1 silencing significantly reduced ASFV replication, indicating its proviral role. Given BANF1's established function in regulating the cGAS/STING-dependent type I interferon (IFN-I) response, we postulated that A151R and MGF360-21R could inhibit this pathway. Using different strategies, we showed that both A151R and MGF360-21R did indeed inhibit IFN-I induction. Generation of ASFV deficient of A151R or MGF360-21R showed that both mutant viruses enhanced the host IFN response in primary porcine macrophages compared to wild-type virus. However, their capacity to inhibit this pathway could occur through mechanisms independent of BANF1. Proteomic analysis of BANF1 interactors during ASFV in...