Marek’s disease virus: mechanistic insights into host immune responses and multilayered immune evasion strategies

Abstract

ABSTRACT Marek’s disease virus (MDV) is a highly contagious, oncogenic alphaherpesvirus that induces profound immunosuppression and T-cell lymphomas in poultry, serving as a prominent paradigm for investigating virus-induced tumorigenesis and pathogen evolution under vaccine-driven selection pressure. Despite half a century of widespread vaccination, the continuous circulation and progressive enhancement of MDV virulence within flocks highlight a critical gap in our understanding of host-virus immunological interplay and co-evolution. This review systematically delineates the dynamic molecular mechanisms underlying the interplay between MDV and the host immune system. We first dissect the innate immune sensing networks, with a particular focus on the cGAS-STING pathway, and elucidate the multidimensional strategies employed by MDV to antagonize these early antiviral defenses. Subsequently, we explore the complexities of the adaptive immune response, revealing the immune evasion mechanisms by which MDV establishes a tumor-permissive microenvironment via the downregulation of MHC-I, induction of T-cell exhaustion, and recruitment of regulatory T cells. Furthermore, we discuss telomere integration as a key mechanism contributing to MDV persistence and highlight the unresolved mechanisms governing reactivation. The purpose of this review is to clarify the key factors that determine the immune protective efficacy of MDV vaccines and to provide insights into the optimization of prevention and control strategies.