Transcriptomic Analysis of MGF360–4L Mediated Regulation in African Swine Fever Virus-Infected Porcine Alveolar Macrophages

African swine fever (ASF) is a highly contagious and virulent infectious disease caused by the African swine fever virus (ASFV), with mortality rates approaching 100% in domestic pigs. The global spread of ASF has caused enormous losses to the swine industry and species diversity, seriously affecting food safety in China. ASFV mainly infects the mononuclear system, inducing significant alterations in host-cell gene expression. Multigene family 360 (MGF360) genes play crucial roles in ASFV infection. To investigate the function of MGF360-4L, this study employed high-throughput RNA sequencing to analyze dynamic transcriptomic changes in porcine alveolar macrophages (PAMs) infected with wild-type ASFV (ASFV-WT) or MGF360-4L deletion mutant (ASFVΔMGF360-4L). Results demonstrated that both viruses activated host innate immune responses during early infection, significantly upregulating immune-related genes. At 16 h post-infection, differentially expressed genes in ASFV-WT- and ASFVΔMGF360-4L-infected cells were enriched in aminoacyl-tRNA biosynthesis pathways, suggesting a potential involvement of MGF360-4L in this process. This study elucidates novel ASFV-host interactions using transcriptomics, providing data to support ASF control strategies.