Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
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Published:2023-11-11
Issue:22
Volume:24
Page:16216
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Ramphan Suwipa1, Chumchanchira Chanida2, Sornjai Wannapa1, Chailangkarn Thanathom3ORCID, Jongkaewwattana Anan3ORCID, Assavalapsakul Wanchai4ORCID, Smith Duncan R.1ORCID
Affiliation:
1. Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand 2. Department of Biology, Faculty of Sciences, Chiang Mai University, Chiang Mai 50200, Thailand 3. National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand 4. Department of Microbiology, Faculty of Sciences, Chulalongkorn University, Bangkok 10330, Thailand
Abstract
Zika virus (ZIKV) is a mosquito-transmitted virus that has emerged as a major public health concern due to its association with neurological disorders in humans, including microcephaly in fetuses. ZIKV infection has been shown to alter the miRNA profile in host cells, and these changes can contain elements that are proviral, while others can be antiviral in action. In this study, the expression of 22 miRNAs in human A549 cells infected with two different ZIKV isolates was investigated. All of the investigated miRNAs showed significant changes in expression at at least one time point examined. Markedly, 18 of the miRNAs examined showed statistically significant differences in expression between the two strains examined. Four miRNAs (miR-21, miR-34a, miR-128 and miR-155) were subsequently selected for further investigation. These four miRNAs were shown to modulate antiviral effects against ZIKV, as downregulation of their expression through anti-miRNA oligonucleotides resulted in increased virus production, whereas their overexpression through miRNA mimics reduced virus production. However, statistically significant changes were again seen when comparing the two strains investigated. Lastly, candidate targets of the miRNAs miR-34a and miR-128 were examined at the level of the mRNA and protein. HSP70 was identified as a target of miR-34a, but, again, the effects were strain type-specific. The two ZIKV strains used in this study differ by only nine amino acids, and the results highlight that consideration must be given to strain type variation when examining the roles of miRNAs in ZIKV, and probably other virus infections.
Funder
Thailand Research Fund Mahidol University Mahidol University Research Assistantship
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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