microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection

• Vector-mediated miRNA ablation reveals biological impact during virus infection
• Prolonged loss of miRNAs results in dramatic changes to the host transcriptome
• miRNA-mediated activity requires kinetics that exceed the acute response to virus
• miRNA function is generally limited to cytokine levels in response to RNA viruses

SummaryWith the capacity to fine-tune protein expression via sequence-specific interactions, microRNAs (miRNAs) help regulate cell maintenance and differentiation. While some studies have also implicated miRNAs as regulators of the antiviral response, others have found that the RISC complex that facilitates miRNA-mediated silencing is rendered nonfunctional during cellular stress, including virus infection. To determine the global role of miRNAs in the cellular response to virus infection, we generated a vector that rapidly eliminates total cellular miRNA populations in terminally differentiated primary cultures. Loss of miRNAs has a negligible impact on both innate sensing of and immediate response to acute viral infection. In contrast, miRNA depletion specifically enhances cytokine expression, providing a posttranslational mechanism for immune cell activation during cellular stress. This work highlights the physiological role of miRNAs during the antiviral response and suggests their contribution is limited to chronic infections and the acute activation of the adaptive immune response.

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