Inhibition of Influenza a Virus Replication by a Mammalian Specific Small Rna

The influenza A virus has been a global public health concerns since the Spanish flu oubreak in the1918s; however, broad-spectrum antiviral drug and effective treatments have not yet been fully developed because flu virus has high mutation rate that would generate drug-resistant virus. Here we would like to use microRNA antagonist as an antiviral agent. Numerous studies have shown that miRNA affects virus replication by regulating viral or cellular gene expression, indicating that miRNA might regulate mutiple gene expressions to control virus growth. In our preliminary results, we identified human-specific hsa-miR-1290 as a positive regulator of influenza A virus replication and the viral titers decreased when we over-expressed the hsa-miR-1290 inhibitor in cells. This proposal focuses on the mechanism that influenza-A-virus-inducing hsa-miR-1290 and hsa-miR-1290 promotes influenza A virus replication. In addition, hsa-miR-1290 is a human-specific miRNA that we cannot study further in mouse models; therefore, we will estabilish a primary human respiratory epithelial cell culture system to conduct additional studies. We anticipate that the hsa-miR-1290 inhibitor will be a feasible broad-spectrum and effective antiviral drug. In addition, the human-specific hsa-miR-1290 could facilitate exploring additional human-specific factors invoved in influenza A virus replication, which could explain why some influenza A virus strains have more severe symptoms in humans than in birds or other animals. The following are the 4 specific aims in the proposal: Aim 1: To study the mechanism of the influenza A virus that induces hsa-miR-1290 expression. Aim 2: Examine whether hsa-miR-1290 promotes influenza A virus replication by targeting the viral genome. Aim 3: Examine whether hsa-miR-1290 promotes influenza A virus replication by targeting cellular genes. Aim 4: Validate regulation of hsa-miR-1290 on influenza A virsus replication in primary human respiratory epithelial cells.

Project ID:PC10601-0259
External Project ID:MOST104-2320-B182-026-MY3