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GS-9620 inhibits enterovirus 71 replication mainly through the NF-κB and PI3K-AKT signaling pathways.

Author information

1
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China.
2
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China. Electronic address: ljn_zb03038@126.com.
3
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China. Electronic address: qinchuan@pumc.edu.cn.

Abstract

Human enterovirus 71 (EV71) is the second most common cause of hand, foot, and mouth disease (HFMD), which can occur as a severe epidemic especially among children under 5-years old. New and improved treatment strategies to control EV71 infection are therefore urgently required. The heterocyclic compound GS-9620, a potent and selective agonist of Toll-like receptor 7 (TLR7), has been reported to activate plasmacytoid dendritic cells (pDCs), and suppress HBV as well as HIV replication. In this study, we indicated that GS-9620 also could inhibit EV71 replication in the mouse model of EV71 infection. With three-days treatment after EV71 infection, the levels of proinflammatory cytokines/chemokines, like IFN-α, IFN-γ and MCP-1, were sharply reduced in serum compared to those without treatment. Furthermore, GS-9620 activated TLR7 in the limb muscle cells, which stimulated the NF-κB and PI3K/AKT signaling pathways. When NF-κB or PI3K/AKT inhibitors were used, the antiviral effect of the GS-9620 was impacted. Overall, our data implied GS-9620 probably activates NF-κB and PI3K/AKT signaling pathways to clear the virus.

KEYWORDS:

Enterovirus 71; Foot and mouth disease; GS-9620; Hand; NF-κB and PI3K-AKT signaling pathways


原文链接:https://www.ncbi.nlm.nih.gov/pubmed/29425831