Medicine and Health Sciences Commons^™

Inactivation Of Type I Ifn Jak-Stat Pathway In Ebv Latency, Shunbin Ning, Ling Wang

ETSU Faculty Works

Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet …

Expansion Of Myeloid-Derived Suppressor Cells Promotes Differentiation Of Regulatory T Cells In Hiv-1+ Individuals, Ling Wang, Juan Zhao, Junping P. Ren, Xiao Y. Wu, Zheng D. Morrison, Mohamed A. El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Objective: Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood.

Design: In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ Tregs.

Methods: We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by coculturing experiments.

Results: We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy with undetectable viremia, …

Protein Phosphatase 1 Abrogates Irf7-Mediated Type I Ifn Response In Antiviral Immunity, Ling Wang, Juan Zhao, Junping Ren, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN‐α in response to viral infection, and phosphorylation at IRF7 C‐terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)‐binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε‐stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and …

Hcv-Induced Mir146a Controls Socs1/Stat3 And Cytokine Expression In Monocytes To Promote Regulatory T-Cell Development, Junping Ren, Rue S. Ying, Yong Q. Cheng, Ling Wang, Mohamed A. El Gazzar, Guang Y. Li, Shun B. Ning, Jonathon P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up‐regulated in monocytes from hepatitis C virus (HCV )‐infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll‐like receptor (TLR ) stimulation. This miR146a induction by HCV infection …