Immune evasion in classical swine fever: Viral modulation of antigen-presentation pathways

Abstract

Classical swine fever remains a major threat to global pig production systems, despite decades of sustained control endeavours. Its causative agent classical swine fever virus (CSFV) employs a highly coordinated set of immune evasion mechanisms to weaken host antiviral defences and permit extensive viral replication. A central focus of this strategy is the antigen-presentation machinery, where CSFV disrupts both major histocompatibility complex class (MHC)-I and MHC-II pathways in macrophages and dendritic cells, which are its primary immune cell reservoirs. By suppressing interferon signaling, dysregulating NF-kB activation, and impairing the maturation of antigen-presenting cells, CSFV compromises peptide processing, co-stimulatory signaling, and T-cell priming. These defects propagate through the adaptive immune system, leading to delayed cytotoxic responses, inadequate CD4 + T-cell help, and impaired humoral immunity. CSFV simultaneously reshapes macrophage polarization, drives profound dendritic cell dysfunction, induces lymphoid apoptosis, and modulates γδ T-cell activity in a manner that correlates with viral virulence. In addition, viral remodeling of intracellular organelles further limits antigen presentation and exacerbates immunopathology. Together, these interconnected mechanisms create a permissive cellular environment that facilitates viral persistence and amplifies disease severity. Understanding how CSFV manipulates antigen-presentation pathways provides crucial insights for the design of next-generation vaccines and therapeutic strategies capable of restoring robust antiviral immunity.