HTNV-induced upregulation of miR-146a in HUVECs promotes viral infection by modulating pro-inflammatory cytokine release
- State Key Laboratory of Virology, Institute of Medical Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Wuhan 430071, Hubei Province (China)
- Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province (China)
- School of Basic Medicine, Hubei University of Science and Technology, No.88 Xianning Avenue, Xianning 437100, Hubei Province (China)
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, No.300 Guangzhou Road, Nanjing 210029, Jiangsu Province (China)
- Institute of Military Medical Sciences Nanjing Command, Nanjing 210002, Jiangsu Province (China)
Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-κB (NF-κB) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-β). Moreover, miR-146a exhibited a negative regulatory effect on the NF-κB pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-β, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection. - Highlights: • Hantavirus infection increased miR-146a levels in HUVEC cells. • Hantavirus infection activated NF-κB signal and pro-inflammatory cytokines in HUVEC cells. • miR-146a had the negative regulation to NF-κBp65, IL-8, CCL5, IP-10, and IFN-β and promote the replication of hantavirus. • Expression of hantaviral proteins (NP/GP) stimulated the activity of miR-146a and NF-κB promoters.
- OSTI ID:
- 22719134
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 493, Issue 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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