Human miRNA miR-532-5p exhibits antiviral activity against West Nile virus via suppression of host genes SESTD1 and TAB3 required for virus replication

Slonchak, Andrii, Shannon, Rory P, Pali, Gabor and Khromykh, Alexander A (2016) Human miRNA miR-532-5p exhibits antiviral activity against West Nile virus via suppression of host genes SESTD1 and TAB3 required for virus replication. Journal of Virology, 90 5: 2388-2402. doi:10.1128/JVI.02608-15


Author Slonchak, Andrii
Shannon, Rory P
Pali, Gabor
Khromykh, Alexander A
Title Human miRNA miR-532-5p exhibits antiviral activity against West Nile virus via suppression of host genes SESTD1 and TAB3 required for virus replication
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2016-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1128/JVI.02608-15
Open Access Status DOI
Volume 90
Issue 5
Start page 2388
End page 2402
Total pages 15
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
West Nile virus (WNV) is a mosquito-transmitted flavivirus, which naturally circulates between mosquitos and birds, but can also infect humans causing severe neurological disease. The early host response to WNV infection in vertebrates primarily relies on the type I interferon pathway, however, recent studies suggest that micro RNAs (miRNAs) may also play a notable role. In this study, we assessed the role of host miRNAs in response to WNV infection in human cells. We employed RNASeq analysis to determine changes in the expression of host miRNAs in HEK293 cells infected with an Australian strain of WNV, Kunjin, (WNVKUN) and identified a number of host miRNAs differentially expressed in response to infection. Three of these miRNAs were confirmed to be significantly up regulated in infected cells by qRT-PCR and Northern blot analyses and one of them, miR-532-5p, exhibited a significant antiviral effect against WNVKUN infection. We have demonstrated that miR-532-5p targets and down-regulates expression of the host genes, SESTD1 and TAB3 in human cells. siRNA depletion studies showed that both SESTD1 and TAB3 were required for efficient WNVKUN replication. We have also demonstrated up regulation of mir-532-5p expression and corresponding decrease in the expression of its targets, SESTD1 and TAB3 in the brains of WNVKUN-infected mice. Our results show that up-regulation of miR-532-5p and subsequent suppression of SESTD1 and TAB3 genes represents a host antiviral response aimed at limiting WNVKUN infection and highlight the important role of miRNAs in controlling RNA virus infections in mammalian hosts.

IMPORTANCE West Nile virus (WNV) is a significant viral pathogen, which poses a considerable threat for human health across the globe. There is no specific treatment or licenced vaccine available for WNV and deeper insight into how this virus interacts with the host is required to facilitate their development. In this study we addressed the role of host micro RNAs (miRNA) in antiviral response to WNV in human cells. We identified miR-532-5p as a novel antiviral miRNA and showed that it is up regulated in response to WNV infection and suppresses the expression of host genes TAB3 and SESTD1 required for WNV replication. Our results show that up-regulation of miR-532-5p and subsequent suppression of SESTD1 and TAB3 genes represents an antiviral response aimed at limiting WNV infection and highlights the important role of miRNAs in controlling virus infections in mammalian hosts.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 15 Jan 2016, 21:21:01 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences