Immune Evasion Mechanisms of Feline Herpesvirus 1 (FHV-1) and their implications for next-generation vaccine development

Feline Herpesvirus 1 (FHV-1), an alphaherpesvirus belonging to the family Herpesviridae, is the primary etiological agent of Feline Viral Rhinotracheitis (FVR), causing severe upper respiratory tract and ocular diseases in felids worldwide. Despite the widespread use of conventional vaccines, FHV-1 remains endemic due to its evolutionary capacity to establish life-long latent infections within the trigeminal ganglia and intermittently reactivate under stressful conditions. This persistence is facilitated by a sophisticated array of immune evasion strategies that neutralize both innate and adaptive host immune responses. Crucial to this process are specific viral envelope glycoproteins (gB, gC, gD, gE, gG, gH, and gL) which mediate attachment, fusion, and direct cell-to-cell spread, thereby minimizing exposure to extracellular neutralizing antibodies. Furthermore, FHV-1 actively interferes with host defense mechanisms by downregulating Major Histocompatibility Complex (MHC) Class I expression to escape CD8+ cytotoxic T lymphocyte surveillance and suppressing innate type I interferon (IFN-/) signaling cascades. From a translational perspective, understanding these molecular interactions is vital for upgrading current diagnostic tools and designing next-generation vaccine platforms, including gene-deleted mutants (e.g., thymidine kinase-deficient strains), subunit formulations, and viral-vectored or mRNA technologies. This review comprehensively synthesizes the current knowledge on FHV-1-host immunobiological interactions, structural virulence factors, and latency dynamics, while highlighting critical pathways to overcome the limitations of current vaccinology strategies and achieve sterile immunity.