期刊
VIRUSES-BASEL
卷 12, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/v12010009
关键词
West Nile virus; micro-RNAs; miR-155; immune response; inflammatory cytokines and chemokines; virus replication
类别
资金
- National Institute of Neurological Disorders and Stroke [R21NS099838]
- Office of the Director, National Institutes of Health [R21OD024896]
- Hawaii Community Foundation [18CON-90812]
West Nile virus (WNV) is a flavivirus that has disseminated globally as a significant cause of viral encephalitis in humans. MircoRNA-155 (miR-155) regulates various aspects of innate and adaptive immune responses. We previously reported that WNV infection induces upregulation of miR-155 in mice brains. In the current study, we demonstrate the critical role of miR-155 in restricting the pathogenesis of WNV infection in mice. Compared to wild-type (WT) mice, miR-155 knockout mice exhibited significantly higher morbidity and mortality after infection with either a lethal strain, WNV NY99, or a non-lethal strain, WNV Eg101. Increased mortality in miR-155(-/-) mice was associated with significantly high WNV burden in the serum and brains. Protein levels of interferon (IFN)-alpha in the serum and brains were higher in miR-155(-/-) mice. However, miR-155(-/-) mice exhibited significantly lower protein levels of anti-viral interleukin (IL)-1 beta, IL-12, IL-6, IL-15, and GM-CSF despite the high viral load. Primary mouse cells lacking miR-155 were more susceptible to infection with WNV compared to cells derived from WT mice. Besides, overexpression of miR-155 in human neuronal cells modulated anti-viral cytokine response and resulted in significantly lower WNV replication. These data collectively indicate that miR-155 restricts WNV production in mouse and human cells and protects against lethal WNV infection in mice.
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