MicroRNAs Regulate Response to Chronic Viral Infections

To study the role of microRNAs (miRNAs) in the cellular response to virus infection, researchers generated a vector that rapidly eliminated total cellular miRNA.

MicroRNAs are a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation. While some studies have also implicated miRNAs as regulators of the antiviral response, others have found that RISC (RNA-induced silencing complex), which 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, investigators at the Icahn School of Medicine at Mount Sinai (New York, NY, USA) generated a poxvirus gene vector that rapidly eliminated total cellular miRNA populations in terminally differentiated primary cultures.

They reported in the December 9, 2015, issue of the journal Cell Host & Microbe that loss of miRNAs had a negligible impact on both innate sensing of and immediate response to acute viral infection. In contrast, miRNA depletion specifically enhanced cytokine expression, providing a posttranslational mechanism for immune cell activation during cellular stress.

Overall, the results highlighted the physiological role of miRNAs during the antiviral response and suggested that their contribution was limited to chronic infections and the acute activation of the adaptive immune response.

“Apart from their roles in causing medical maladies, viruses have long been used as tools to reveal unappreciated aspects of biology, providing us with insights into the many unknowns of how our cells function,” said senior author Dr. Benjamin tenOever, professor of microbiology at the Icahn School of Medicine at Mount. “We developed a tool based on a poxvirus gene that allows us to manipulate microRNA populations in any tissue or cell type we desire.”

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Icahn School of Medicine at Mount Sinai