The interaction between Marek's disease virus pUL11 and pUL56 antagonizes STING-mediated IFN-β production in cultured chicken cells.

Marek's disease virus (MDV) is a notorious agent for malignant T cell lymphomas in chickens, and has evolved viral homologs that functionally differ from its counterparts of closely related herpesvirus species. Unlike the structural proteins that make up infectious virions, the functions of many MDV tegument proteins remain less characterized. For mammalian herpesviruses, two highly conserved tegument proteins pUL11 and pUL56 have been functionally identified, and shown to interact with each other. However, little is known about the interaction between their homologs of MDV, particularly whether they play a role in subverting innate immune response. In this study, the putative interaction between MDV pUL11 and pUL56 was determined by confocal immunofluorescence and co-immunoprecipitation assays. When overexpressed alone, MDV pUL11 was predominantly localized in the Golgi complex. By transfection of MDV pUL56 variants containing mutations in critical motifs, the late domains of MDV pUL56 were found indispensable for its binding to MDV pUL11, whereas their interaction was kept intact despite the absence of the single transmembrane domain (TMD) within MDV pUL56. Interestingly, MDV pUL11 served as an efficient partner that facilitated the nuclear export of the TMD-deletion pUL56 mutant. Furthermore, the induction of chicken IFN-β with a STING agonist was significantly impaired in the context of MDV pUL11 and pUL56 co-expression. This study highlights the broader conservation of interacting partners across cognate herpesviruses, and provides the evidence that MDV pUL11 and pUL56 collaborate to counteract innate immune signaling.