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

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.

Glycolysis is reduced in dengue virus 2 infected liver cells

“…Collectively these results point to both virus strain and cell type in being variables that can modulate the results. In a recent study we showed that two Zika virus strains differing by only 9 amino acid changes interacted in markedly distinct way with the host cell miRNA machinery 42 . We previously published an analysis of the protein changes induced by 12 DENVs of different serotypes and origin (DENV 1–4; low passage isolates from dengue fever, low passage isolates from dengue hemorrhagic fever and laboratory adapted isolates).…”

The Role of Noncoding RNA in the Transmission and Pathogenicity of Flaviviruses

“…miRNAs may exhibit differential regulatory effects across diverse viruses. Specifically, miR-21 enhances the replication of DENV while exhibiting antiviral effects against ZIKV [ 59 , 60 ]. Further investigation is required to elucidate the mechanisms by which miR-21 regulates flaviviral replication.…”