Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection

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 e...

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Main Authors: Suwipa Ramphan, Chanida Chumchanchira, Wannapa Sornjai, Thanathom Chailangkarn, Anan Jongkaewwattana, Wanchai Assavalapsakul, Duncan R. Smith
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/22/16216
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author Suwipa Ramphan
Chanida Chumchanchira
Wannapa Sornjai
Thanathom Chailangkarn
Anan Jongkaewwattana
Wanchai Assavalapsakul
Duncan R. Smith
author_facet Suwipa Ramphan
Chanida Chumchanchira
Wannapa Sornjai
Thanathom Chailangkarn
Anan Jongkaewwattana
Wanchai Assavalapsakul
Duncan R. Smith
author_sort Suwipa Ramphan
collection DOAJ
description 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.
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spelling doaj.art-7af56d831b7e4aca85afb173d23678772023-11-24T14:46:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221621610.3390/ijms242216216Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus InfectionSuwipa Ramphan0Chanida Chumchanchira1Wannapa Sornjai2Thanathom Chailangkarn3Anan Jongkaewwattana4Wanchai Assavalapsakul5Duncan R. Smith6Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, ThailandDepartment of Biology, Faculty of Sciences, Chiang Mai University, Chiang Mai 50200, ThailandInstitute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, ThailandDepartment of Microbiology, Faculty of Sciences, Chulalongkorn University, Bangkok 10330, ThailandInstitute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, ThailandZika 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.https://www.mdpi.com/1422-0067/24/22/16216ZIKVmicroRNAmiRNAmiR-34aheat shock protein 70 kDaHSP70
spellingShingle Suwipa Ramphan
Chanida Chumchanchira
Wannapa Sornjai
Thanathom Chailangkarn
Anan Jongkaewwattana
Wanchai Assavalapsakul
Duncan R. Smith
Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
International Journal of Molecular Sciences
ZIKV
microRNA
miRNA
miR-34a
heat shock protein 70 kDa
HSP70
title Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
title_full Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
title_fullStr Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
title_full_unstemmed Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
title_short Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
title_sort strain variation can significantly modulate the mirna response to zika virus infection
topic ZIKV
microRNA
miRNA
miR-34a
heat shock protein 70 kDa
HSP70
url https://www.mdpi.com/1422-0067/24/22/16216
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