MicroRNA‐155 inhibits dengue virus replication by inducing heme oxygenase‐1‐mediated antiviral interferon responses

Abstract

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus–host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR‐155 time‐dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR‐155 appeared to limit viral replication in vitro, suggesting that the low levels of miR‐155 would be beneficial for DENV replication. In vivo, overexpression of miR‐155 protected ICR suckling mice from the life‐threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti‐DENV activity of miR‐155 was due to target Bach1, resulting in the induction of the heme oxygenase‐1 (HO‐1)‐mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon‐induced protein kinase R (PKR), 2′‐5′‐oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR‐155 expression.

(E)-Guggulsterone Inhibits Dengue Virus Replication by Upregulating Antiviral Interferon Responses through the Induction of Heme Oxygenase-1 Expression

“…Our results indicate that (E)-guggulsterone effectively hinders the DENV replication (Figure 1) and upregulates DENV-reduced HO-1 expression (Figure 2) in a dose-dependent manner. This finding is consistent with our previous studies showing that the HO-1 inducers lucidone and microRNA-155 inhibit DENV replication [13,24], which is comparable with the results of genetic knockdown by HO-1 shRNA that attenuated the antiviral effects of (E)-guggulsterone (Figure 2d). Another study demonstrated that DENV NS2B/NS3 protease, a vital protein for DENV replication [25], interferes with the antiviral IFN signaling pathway [22].…”

The Role of Non-coding RNAs in Viral Myocarditis

“…It has been proven that the replication process is indispensable in the viral life cycle, so inhibiting this process may help to block VMC in the early stages. Undoubtedly, many miRNAs are involved in this process ( Table 1 ; Sodroski et al, 2019 ; Su et al, 2020 ). MiRNAs have two patterns to regulate viral replication: one is the direct pattern, and the other is the indirect pattern.…”

microRNAs, the Link Between Dengue Virus and the Host Genome

“…Another study showed that the antiviral effects of HO-1 are related to the recovery of the antiviral IFN immune response signal pathway and the inhibition of DENV protease activity by biliverdin, a byproduct of heme degradation catalyzed by HO-1 ( Tseng et al, 2016 ). A recent study found that overexpression of miR-155 in Huh-7 cells inhibits virus replication in vitro ( Su et al, 2020 ). In vivo , overexpression of miR-155 can protect ICR suckling mice from the threat of DENV infection, and miR-155 also induces HO-1-mediated antiviral response by targeting BACH1 ( Su et al, 2020 ).…”

“…A recent study found that overexpression of miR-155 in Huh-7 cells inhibits virus replication in vitro ( Su et al, 2020 ). In vivo , overexpression of miR-155 can protect ICR suckling mice from the threat of DENV infection, and miR-155 also induces HO-1-mediated antiviral response by targeting BACH1 ( Su et al, 2020 ). Finally, the HO-1-mediated inhibition of NS2B/NS3 protease activity enhances induction of antiviral interferons and inhibits virus replication ( Su et al, 2020 ).…”