Format

Send to

Choose Destination
Cell Death Dis. 2018 Jan 24;9(2):104. doi: 10.1038/s41419-017-0122-4.

The cytomegalovirus protein US31 induces inflammation through mono-macrophages in systemic lupus erythematosus by promoting NF-κB2 activation.

Author information

1
Department of Microbiology and Immunology, Institute of molecular virology and immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, China.
2
Second Clinical College, Wenzhou Medical University, Wenzhou, China.
3
Department of Pathophysiology, Wenzhou Medical University, Wenzhou, China.
4
Department of Laboratory Medicine, Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
5
Cardiac regeneration research institute, Wenzhou Medical University, Wenzhou, China.
6
Department of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
7
Department of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. hdzhang@163.com.
8
Department of Microbiology and Immunology, Institute of molecular virology and immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, China. wzxxy001@163.com.

Abstract

It has been hypothesized that human cytomegalovirus (HCMV) infection, especially in monocyte and CD34 (+) myeloid cells, acts as a important regulator of immune system to promote inflammation in multiple autoimmune diseases. The aim of 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. 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. Taken together, 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. Our findings provide a foundation for the continued investigation of novel therapeutic targets for SLE patients.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center