Table 1.
Characteristics and main findings of the studies investigating epigenetic markers associated with arbovirus infections in humans.
| References | Virus | Study type | Epigenetic alteration | Results | Cell line |
|---|---|---|---|---|---|
| Bayer et al., (43) | ZIKV | in vitro | chromosome 19 microRNA cluster overexpression | C19MC miRNAs limit ZIKV infection | human throphoblasts |
| Bogerd et al. (19) | WNV and DENV | in vitro | Dicer mRNA | DENV and WNV do not express any viral miRNAs in human cells and neither DENV nor WNV induce the production of viral siRNAs in infected human somatic cells | Huh7 cells, a type of human liver cell line |
| Casseb et al. (29) | DENV | in vitro | Drosha, DGCR8, and Dicer mRNAs | Drosha, DGCR8, and Dicer mRNAs are down-regulated in human cells infected with DENV-4 | epithelial cells |
| Chen et al. (20) | DENV | in vivo | miR-150 overexpression | reduced SOCS1 expression was significantly associated with up-regulated miR-150 levels | peripheral blood mononuclear cells |
| Colpitts et al. (13) | DENV | in vitro | Nuclear histone proteins H2A, H2B, H3 and H4 as target of the capsid protein of the virus | All four core histones were pulled out of the cell lysates by DEN2 C and were identified with high percent coverage and low expectation values | Huh7 cells, a type of human liver cell line |
| Demir et al. (37) | CCHFV | in vivo | downregulation of miR-146a and upregulation of miR-451 and miR-31 | downregulation od miR-146aand upregulation of hsa-miR-451 and hsa-miR-31 leads to augmentation of proinflammatory cytokines | peripheral blood mononuclear cells |
| Devhare et al. (38) | ZIKV | in vitro | reduced p53 phosphorylation | ZIKV strains induce human neural stem cells (hNSC) growth inhibition and display distinct E glycoprotein localization | human neural stem cells |
| Diosa-Toro et al. (39) | DENV | in vitro | miR-3614-5p overexpression | miR-3614-5p regulated ADAR1 expression, a protein that facilitates viral replication | primary human macrophage |
| Escalera-Cueto et al. (24) | DENV | in vitro | miRNA Let-7 overexpression | Let-7c has an antiviral effect through the modulation of BACH1 and HO-1 | Huh7 cells, a type of human liver cell line |
| Gomes et al. (30) | DENV | in vivo | Methylation of cytokine genes | Significant frequency of demethylation in the region of the TNF-a promoter in DENV infected patients | Total RNA was isolated from whole blood |
| Kakumani et al. (31) | DENV | in vitro | human microRNA mir-126 | The chaperone and the miRNA, hsa-mir-126-5p restricts dengue virus replication in human cell lines | Huh7 cells, a type of human liver cell line |
| Kakumani et al. (15) | DENV | in vitro | RNAi suppression | Downregulation of iRNA factors as Dicer, Drosha, Ago1 and Ago2. Also, NS4B, a viral protein, as a RNAi supressor. | Huh 7 and HEK293T (human embryonic kidney cells) |
| Kakumani et al. (25) | DENV | in vitro | RNAi suppression | DENV non-structural protein 3 suppresses human miRNA machinery | human embryonic kidney (HEK) HEK293T cells |
| Kanokudom et al. (40) | DENV | in vitro | microRNA 21 overexpression | miR-21 is significantly increased upon DENV 2 infection and that expression of this miRNA promotes DENV replication | HepG2 cells, a human liver cancer cell line |
| Kozak et al. (41) | ZIKV | in vitro | miR-30e-3p, miR-30e-5p, miR-17-5p | induction of genetic pathway of autophagy including CHOP and GADD34 | astrocytes |
| Kumari et al. (32) | JEV | in vitro | miR-34c-5p suppression | miR-34c-5p which is suppressed during JEV infection and overexpression of this miRNA modulates JEV induced proinflammatory cytokine production | human microglial cells |
| Lichinchi et al. (33) | ZIKV | In vitro | human m6A RNA | m6A RNA Methylation Modulates the ZIKV Life Cycle | human HEK293T cells |
| Liu et al. (34) | DENV | In vivo | miR-27a*, miR-30e, and miR-378 were down-regulated | miR-378, but not miR-27a* or miR-30e, suppressed GrzB expression in NK cells | NK cells |
| Ouyang et al. (35) | DENV | In vivo | miR-21-5p, miR-590-5p, miR-188-5p, and miR-152-3p overexpression, whereas miR-146a-5p was down-regulated | miR-21-5p and miR-146a-5p could distinguish dengue-infected patients with preferable sensitivity and specificity | Total RNA was isolated from whole blood |
| Pham et al. (14) | DENV | In vitro | miR-142 incorporation | Incorporation of miR-142 target sites into the 3UTR of DENV-2 confers endogenous attenuation of the virus in a cell-specific manner | human fibroblasts |
| Pu et al. (42) | DENV | In vitro | miR-146a overexpression | miR-146a significantly blocked DENV2-induced autophagy | A549 cells (adenocarcinoma human alveolar basal epithelial cells) and THP-1 cells (a human monocytic cell line) |
| Qi et al. (16) | DENV | In vivo | miR-4290,−4279,−625*, -let-7e,−1290,−33a,−378,−1246,−767-5p,−320c,−720,−491-3p,−3647,−451 and−4286, miR-106b,−20a,−30b and−3653 | Upregulated miRNA subsets included: miR-4290,−4279,−625*, -let-7e,−1290,−33a,−378,−1246,−767-5p,−320c,−720,−491-3p,−3647,−451 and−4286.Downregulated miRNA subsets included: miR-106b,−20a,−30b and−3653 | peripheral blood mononuclear cells |
| Rastogi et al. (44) | JEV | In vitro | 48 differentially expressed microRNAs26/02/2018 34 are significantly up regulated and 14 are down regulated | miR-32-5p is up regulated in JEV infected human microglia with respect its pleiotropic to control. KLF4 (Kruppel-like-factor 4) gene was predicted as one of its target. The down-regulation of miR-432-5p and NEDD4L (neural precursor cell expressed developmentally down-regulated protein 4) has been identified as one of the potential target as well | human microglial cells |
| Saxena et al. (17) | CHIKV | In vitro | miR-744, miR-638, miR-503 | miRNA expression profiling revealed regulation of 152 miRNAs post CHIKV infection | HEK293T cells |
| Selvamani et al. (21) | CHIKV | In vitro | miR-146a overexpression | CHIKV infection induced the expression of cellular miR-146a, which resulted into down-regulation of TRAF6, IRAK1, IRAK2 and increased replication of CHIKV in human synovial fibroblasts. Downregulation of TRAF6, IRAK1 and IRAK2 led to downstream decreased NF-kB activation through negative feedback loop | Human Synovial Fibroblasts |
| Sharma et al. (26) | JEV | In vitro | miR146-a overexpression | Exogenous overexpression of miR-146a led to suppression of NF-κB activation and abrogation of Jak-STAT pathway upon JEV infection which led to downregulation of interferon-stimulated genes (IFIT-1 and IFIT-2) and facilitated viral replication | human microglial cells |
| Slonchak et al. (27) | WNV | In vitro | miR-532-5p overexpression | miR-532-5p exhibits antiviral activity against West Nile virus via suppression of host genes SESTD1 and TAB3 required for virus replication | Human embryonic kidney cells (HEK293) |
| Tambyah et al. (36) | DENV | In vivo | Overexpression of a cluster of 12 miRNA (miR-450b-5p,−491-5p,−499a-3p,−512-5p,−615-5p,−624-5p,−892b,−1204,−1225-5p,−3121-3p,−4259 and−4327) | Expression patterns of 12 miRNAs (miR-450b-5p,−491-5p,−499a-3p,−512-5p,−615-5p,−624-5p,−892b,−1204,−1225-5p,−3121-3p,−4259 and−4327) were seen to be significant and specific for acute dengue cases. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation. | Total RNA was isolated from whole blood |
| Wu et al. (22) | DENV | In vitro | miR-223 overexpression | miR-223 overexpression controls DENV-2 replication by negatively regulating microtubule destabilizer STMN1 gene | EAhy926 cells, a human vascular endothelial line |
| Wu et al. (18) | DENV | In vitro | miR-146a overexpression | miR-146a facilitates DENV replication by targeting TRAF6 and consequently reducing IFN-B levels | human monocytic cell THP-1, a model for human monocytes |
| Zhu et al. (28) | JEV | In vitro | MicroRNA-15b overexpression | miR-15b Modulates JEV– mediated Inflammation via Targeting RNF125 | human astrocytoma cell and HeLa cells |
| Zhu et al. (23) | DENV | In vitro | induction of MicroRNA-30e* | miR-30e* Suppresses DENV Replication by promoting NF-kB–Dependent IFN Production | human monocyte cell line U937 |