FP077THE CYTOMEGALOVIRUS PROTEIN US31 INDUCES INFLAMMATION THROUGH MONO-MACROPHAGES IN SYSTEMIC LUPUS ERYTHEMATOSUS BY PROMOTING NF-κB2 ACTIVATION

INTRODUCTION AND AIMS: This study was to elucidate the HCMV gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of SLE patients and demonstrate the effect and mechanism of viral gene associated with SLE in mono-macrophages functions. METHODS: High-throughput RNA-Seq techniques in combination with RT-PCR were used to explore the profile of HCMV gene expression in the PBMCs of SLE patient. Transcriptome sequencing and RT-qPCR combing with consequent bioinformatics analysis were used to explore the effects of US31 expression on the function of THP-1 monocytes and THP-1-derived macrophages. To identify the molecular mechanism of US31 during inflammation, a customized protein binding array were used to screen the potential US31-interacting proteins and then confirmed by Co-IP and Western blot. RESULTS: Using two RNA-Seq techniques in combination with RT-PCR, 11 viral genes mainly associated with latent HCMV infection were identified in the PBMCs of SLE patients. Among these viral genes, US31 with previously unknown function was highly expressed in the PBMCs of SLE patients compared to healthy controls. Analysis of function indicated that US31 expression could induce inflammation in monocyte and macrophage and stimulate macrophage differentiation toward an M1 macrophage phenotype. Screening via protein chips in combination with bioinformatic analysis and consequent detection of mono-macrophages function indicates that the direct interaction between US31 and NF-κB2 contributed the NF-kB2 activation. Consequent analysis indicated US31 directly interacted with NF-κB2, contribute to the polyubiquitination of the phosphorylated p100 and consequent activation of NF-κB2. CONCLUSIONS: Our data uncovered a previously unknown role of the HCMV protein US31 in inducing NF-κB-mediated mono-macrophage inflammation in the pathogenesis and development of SLE.