article · Virology Journal
Influenza A virus relies on host cellular mechanisms to replicate, often overcoming the body's natural interferon antiviral defences. This study investigated how a specific host molecule, microRNA-141, influences influenza A virus replication and interferon signalling in human lung cells. Infection with various influenza A virus strains caused a significant rise in microRNA-141 levels. Artificially increasing microRNA-141 boosted viral replication and suppressed critical antiviral genes and proteins, including MxA, STAT3, IFI27, and LAMP3, as well as reducing interferon-beta production. Conversely, blocking microRNA-141 with an inhibitor restored MxA and STAT3 expression, raised interferon-beta levels, and strongly interrupted viral replication. These findings demonstrate that influenza A virus relies on microRNA-141 to suppress interferon-mediated immune pathways, highlighting microRNA-141 as an essential host factor that supports viral replication by downregulating host immune responses.
Influenza A remains a major global respiratory health concern with the ability to evade host immune responses. Understanding how the virus exploits host microRNAs to suppress natural defences such as interferon signalling offers clearer biological insights. By identifying microRNA-141 as an enabler of viral replication, this research reveals potential host targets that could be explored to counter viral immune evasion strategies.
This early-stage cellular research points to microRNA-141 inhibitors as potential candidates for host-directed antiviral therapy against influenza A virus. Pharmaceutical researchers and developers targeting respiratory infections could investigate microRNA-141 suppression to restore natural immune defences during infection. However, the findings are based entirely on in vitro laboratory experiments, meaning practical therapeutic use remains at an early discovery stage and requires extensive preclinical testing and in vivo validation.
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The antiviral response against influenza A virus (IAV) infection includes the induction of the interferon (IFN) signaling pathway, including activation of the STATs protein family. Subsequently, antiviral myxovirus resistance (MxA) protein and other interferon-stimulated genes control virus replication; however, the molecular interaction of viral-mediated IFN signaling needs more investigation. Host microRNAs (miRNAs) are small non-coding molecules that posttranscriptionally regulate gene expression. Here, we sought to investigate the possible involvement of miR-141 in IAV-mediated IFN signaling. Accordingly, the microarray analysis of A549 cells transfected with precursor miR-141 (pre-miR-141) was used to capture the potentially regulated genes in response to miR-141 overexpression independent of IAV infection. The downregulation of targeted genes by miR-141, in addition to viral gene expression, was investigated by quantitative real-time PCR, western blot analysis, and flow cytometric assay. Our findings showed a significant upregulation of miR-141 in infected A549 cells with different strains of IAV. Notably, IAV replication was firmly interrupted in cells transfected with the miR-141 inhibitor. While its replication significantly increased in cells transfected with pre-miR-141 confirming the crucial role of miRNA-141 in supporting virus replication. Interestingly, the microarray data of miR-141 transduced A549 cells showed many downregulated genes, including MxA, STAT3, IFI27, and LAMP3. The expression profile of MxA and STAT3 was significantly depleted in infected cells transfected with the pre-miR-141, while their expression was restored in infected cells transfected with the miR-141 inhibitor. Unlike interleukin 6 (IL-6), the production of IFN-β markedly decreased in infected cells that transfected with pre-miR-141, while it significantly elevated in infected cells transfected with miR-141 inhibitor. These data provide evidence for the crucial role of miR-141 in regulating the antiviral gene expression induced by IFN and IL-6 signaling during IAV infection to ensure virus replication.
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DOI: 10.1186/s12985-023-02146-4
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