Computational identification of mutually homologous Zika virus miRNAs that target microcephaly genes

McLean, Ewen; Bhattarai, Roshan; Hughes, Brandon W.; Mahalingam, Kuhanandha; Bagasra, Omar

doi:10.1080/19932820.2017.1304505

Cited by 13 publications

(14 citation statements)

References 38 publications

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“…Previous work already applied some in silico strategy to study the role of the miRNAs during ZIKV infection. However, these studies applied different experimental strategies, models, and ZIKV strains (Azouz et al., 2019; Ferreira et al., 2018; Kozak et al., 2017; McLean et al., 2017; Zhang et al., 2018). In this work, the access to postmortem samples from CZS babies allowed to identify miRNAs modulated by ZIKV directly in human brain tissues.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs 145 and 148a Are Upregulated During Congenital Zika Virus Infection

et al. 2019

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Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) member of the Flaviviridae family, which has been associated with the development of the congenital Zika syndrome (CZS). RNA viruses, such as flaviviruses, have been reported to exert a profound impact on host microRNAs (miRNAs). Cellular miRNAs modulated by ZIKV may help identify cellular pathways of relevance to pathogenesis. Here, we screened 754 human cellular miRNAs modulated by ZIKV infection (Brazilian PE strain) in a neuroblastoma cell line. Seven miRNAs (miR-99a*, miR-126*, miR-190b, miR-361-3p, miR-522-3p, miR-299-5p, and miR-1267) were downregulated during ZIKV infection, while miR-145 was upregulated. Furthermore, 11 miRNAs were exclusively expressed in ZIKV-infected (miR-148a, miR-342-5p, miR-598, and miR-708-3p) or mock cells (miR-208, miR-329, miR-432-5p, miR-488, miR-518b, miR-520g, and miR-767-5p). Furthermore, in silico analysis indicated that some central nervous system, cellular migration, and adhesion function-related biological processes were overrepresented in the list of target genes of the miRNAs regulated in ZIKV-infected cells, especially for miR-145 and miR-148a. The induction of miR-145 and miR-148a was confirmed in postmortem brain samples from stillborn with severe CZS. Finally, we determined the expression regulation of microcephaly related genes through RNA interference pathway caused by ZIKV directly on neuron cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs 145 and 148a Are Upregulated During Congenital Zika Virus Infection

et al. 2019

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“…In the case of ZIKV profound modulations of miRNAs was observed in a chronically infected neuronal cell line. Our sequence-based data suggest that ZIKV-mediated miRNAs appear to modulate a wide range of gene functions in ZIKV-infected neurons, perhaps being responsible for a wide variety of neuronal functions in developing fetal brain that lead to microcephaly and an array of other neurologic illnesses observed in newborns from ZIKV infected mothers [13].…”

Section: Introductionmentioning

confidence: 86%

“…We identified six miRNAs that shared mutual homology to 12 MCPH genetic motifs [12] and hypothesized that ZIKV genes regulated numerous host miRNAs, resulting in miRNA-based modifications of neuronal genetic pathways. miRNAs are small noncoding RNAs that act as gene regulators, acting directly or indirectly on many cellular functions owing to their ability to target mRNAs for degradation or translational repression [13]. Experimental evidence shows that miRNAs have a direct role in different cellular processes, such as immune function, apoptosis, and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of miRNAs in a human developing neuronal cell line chronically infected with Zika virus

Bagasra

Shamabadi

Pandey

et al. 2021

Libyan Journal of Medicine

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Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in affected individuals. The virus can be transmitted from an infected mother to her fetus, via mosquitoes, or sexually. ZIKV infections are associated with increased risk for Guillain-Barré syndrome (GBS) and congenital microcephaly in newborns infected prenatally. Dysregulations of intracellular microRNAs (miRNAs) in infected neurons have been linked to different neurological diseases. To determine the potential role of miRNAs in ZIKV infection we developed a chronically infected neuroblastoma cell line and carried out differential expression analyses of miRNAs with reference to an uninfected neuroblastoma cell line. A total of 3192miRNAs were evaluated and 389 were found to be upregulated < 2-fold and 1291 were downregulated < 2-fold. In particular, we determined that hsa-mir- 431-5p, hsa-mir-3687, hsamir-4655-5p, hsa-mir-6071, hsa-mir-762, hsa-mir-5787, and hsa-mir-6825-3p were significantly downregulated, ranging from -5711 to -660-fold whereas, has- mir-4315, hsa-mir-5681b, hsamir-6511a-3p, hsa-mir-1264, hsa-mir-4418, hsa-mir-4497, hsa-mir-4485-3p, hsa-mir-4715-3p, hsamir-4433-3p, hsa-mir-4708-3p, hsa-mir-1973 and hsa-mir-564 were upregulated, ranging from 20-0.8-fold. We carried out target gene alignment of these miRNAs with the ZIKV genome to predict the function of the differentially expressed miRNAs and their potential impact on ZIKV pathogenesis. These miRNAs might prove useful as novel diagnostic or therapeutic markers and targets for further research on ZIKV infection and neuronal injury resulting from ZIKV infectivity in developing fetal brain neurons.

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“…This gene also encodes a component of the vertebratespecific trithorax H3K4-methylation chromatin remodelling complex that controls central nervous system (CNS) gene expression and cell fate (Yang et al, 2012). ZNF335 is very important for progenitor cell division/differentiation; mutation in this gene leads to the degeneration of neurons, and knockdown of this gene causes a reduction in the size of the brain with a lack of cortex formation as well as disrupted differentiation and proliferation of neuronal cells (McLean et al, 2017). Due to a mutation in ZNF335, MCPH10 was identified in an affected member of an Arab Israeli family.…”

Section: Mcph18-wdfy3mentioning

confidence: 99%

Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH)

et al. 2018

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Primary microcephaly (MCPH) is an autosomal recessive sporadic neurodevelopmental ailment with a trivial head size characteristic that is below 3-4 standard deviations. MCPH is the smaller upshot of an architecturally normal brain; a significant decrease in size is seen in the cerebral cortex. At birth MCPH presents with non-progressive mental retardation, while secondary microcephaly (onset after birth) presents with and without other syndromic features. MCPH is a neurogenic mitotic syndrome nevertheless pretentious patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Eighteen MCPH loci (MCPH1-MCPH18) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6, MFSD2A, ANKLE2, CIT and WDFY3, clarifying our understanding about the molecular basis of microcephaly genetic disorder. It has previously been reported that phenotype disease is caused by MCB gene mutations and the causes of this phenotype are disarrangement of positions and organization of chromosomes during the cell cycle as a result of mutated DNA, centriole duplication, neurogenesis, neuronal migration, microtubule dynamics, transcriptional control and the cell cycle checkpoint having some invisible centrosomal process that can manage the number of neurons that are produced by neuronal precursor cells. Furthermore, researchers inform us about the clinical management of families that are suffering from MCPH. Establishment of both molecular understanding and genetic advocating may help to decrease the rate of this ailment. This current review study examines newly identified genes along with previously identified genes involved in autosomal recessive MCPH.

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Computational identification of mutually homologous Zika virus miRNAs that target microcephaly genes

Cited by 13 publications

References 38 publications

MicroRNAs 145 and 148a Are Upregulated During Congenital Zika Virus Infection

MicroRNAs 145 and 148a Are Upregulated During Congenital Zika Virus Infection

Differential expression of miRNAs in a human developing neuronal cell line chronically infected with Zika virus

Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH)

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