1. Academic Validation
  2. ASFV activates STAT3 to induce proviral M2 macrophage polarization

ASFV activates STAT3 to induce proviral M2 macrophage polarization

  • Vet Microbiol. 2025 Dec:311:110733. doi: 10.1016/j.vetmic.2025.110733.
Yanru Chen 1 Haowei Chen 1 Weijia Zhang 1 Penghao Lv 1 Zhichao Wang 1 Hanlin Liao 1 Kaiyue Wei 1 Qigai He 1 Min Cui 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, China; Hubei Jiangxia Laboratory, Wuhan, China.
  • 2 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, China; Hubei Jiangxia Laboratory, Wuhan, China. Electronic address: [email protected].
Abstract

African swine fever (ASF) is an acute and highly infectious disease caused by African swine fever virus (ASFV) that has dealt a massive blow to the development of the pig industry in China. Macrophages, the primary target cells of ASFV, exhibit high plasticity. However, their phenotypic changes during Infection remain poorly understood. In this study, we observed a significant increase in M2 monocytes within the peripheral blood of ASFV-infected pigs. In vitro experiments demonstrated that ASFV drives macrophage polarization toward the M2 phenotype through early phosphorylation of STAT3. STAT3 inhibition with STATTIC not only blocked M2 polarization but also suppressed ASFV replication. While M2 macrophages do not impede viral attachment or internalization, they display reduced killing capacity compared to M1 macrophages. Furthermore, in a mixed lymphocyte reaction (MLR) system, CD4+ T cells cocultured with ASFV-infected M2-polarized macrophages presented suppressed early activation, marked by downregulated CD25 expression, ultimately impairing adaptive immunity. These findings reveal a critical immune evasion strategy employed by ASFV and provide key insights into ASF pathogenesis and viral persistence.

Keywords

African swine fever virus; Macrophage polarization; Phosphorylation of STAT3.

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