Host-virus interaction: the antiviral defense function of small interfering RNAs can be enhanced by host microRNA-7 in vitro

Abstract

Small interfering RNAs (siRNAs) directed against poliovirus (PV) and other viruses effectively inhibit viral replication and have been developed as antiviral agents. Here, we demonstrate that a specific siRNA targeting the region between nucleotides 100–125 (siRNA-100) from the 5′-untranslated region (5′-UTR) of PV plays a critical role in inhibiting PV replication. Our data demonstrate that siRNA-100 treatment can greatly reduce PV titers, resulting in up-regulation of host microRNA-7 (miR-7), which in turn, leads to enhance inhibition of PV infection further. Moreover, our results suggest that siRNA-100 can also impair the spread of PV to uninfected cells by increasing host resistance to PV, resulting in decreasing necrosis and cytopathic effects (CPE) levels, as well as prolonging the survival of infected cells. Indeed, the active antiviral effect of siRNA-100 was potentially supplemented by the activity of miR-7, and both of them can serve as stabilizing factors for maintenance of cellular homeostasis. Results of this study identify a molecular mechanism of RNAi for antiviral defense, and extend our knowledge of the complex interplay between host and PV, which will provide a basis for the development of effective RNAi-based therapies designed to inhibit PV replication and protect host cells.

MicroRNA-555 has potent antiviral properties against poliovirus

“…High-throughput screening revealed that at least 29 miRNAs were able to inhibit Sabin-2 replication. During the course of this study, other groups reported that PV transcript and protein levels were appreciably lower in ectopic miR-7 expressed in infected A549 cells (Zhang et al, 2015). However, miR-7 was not included in the 29 miRNAs found from our screening data to have antiviral activity.…”

Analysis of the microRNA expression profiles of chicken dendritic cells in response to H9N2 avian influenza virus infection

“…It has been reported that miR-7 is widely conserved in animal species and is up-regulated during invertebrates and vertebrate’s virus infection, such as poliovirus and white spot syndrome virus (WSSV). In crab, the miR-7 could inhibit host anti-viral immune response by targeting Myd88 to enhance WSSV replication [ 21 ], whereas the miR-7 up-regulation induced the inhibition of poliovirus infection in human cells [ 22 ]. Similarly, miR-7 was also found to be up-regulated in human influenza virus infection [ 23 ] and in H9N2 AIV infection in this study.…”

MicroRNA profile analysis of host cells before and after wild human rotavirus infection

“…Changes in miRNA expression in MA104 cells and HT‐29 cells suggest a potential role of miRNAs in antiviral responses. Two recent works showed that miR‐7 could supplement antiviral effect [Zhang et al, ] and miR‐125a plays an important role in HBV infection [Mosca et al, ]. MiR‐7 and miR‐125a maybe has a potential role in anti‐rotavirus response.…”