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

被引:4
|
作者
Ramphan, Suwipa [1 ]
Chumchanchira, Chanida [2 ]
Sornjai, Wannapa [1 ]
Chailangkarn, Thanathom [3 ]
Jongkaewwattana, Anan [3 ]
Assavalapsakul, Wanchai [4 ]
Smith, Duncan R. [1 ]
机构
[1] Mahidol Univ, Inst Mol Biosci, Nakhon Pathom 73170, Thailand
[2] Chiang Mai Univ, Fac Sci, Dept Biol, Chiang Mai 50200, Thailand
[3] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol, Pathum Thani 12120, Thailand
[4] Chulalongkorn Univ, Fac Sci, Dept Microbiol, Bangkok 10330, Thailand
关键词
ZIKV; microRNA; miRNA; miR-34a; heat shock protein 70 kDa; HSP70; CELL-PROLIFERATION; MICRORNAS; REPLICATION; EXPRESSION; RECEPTOR; HEAT-SHOCK-PROTEIN-70; HISTORY; TARGETS;
D O I
10.3390/ijms242216216
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:25
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