Patients with severe cases of influenza sometimes develop Acute Lung Injury (ALI), a highly damaging condition that can be fatal. Treatment options are limited.
MicroRNA (miR) are non-coding RNA molecules that take part in the regulation of gene expression, and they’ve been observed to act abnormally in inflammatory diseases, some forms of cancer and more.
Last summer, third-year veterinary student at The Ohio State University Leon Schermerhorn studied the molecular structure of influenza-induced ALI lung cells and, with his team, was able to conclude that a single miR, miR-155, may play a direct role in the progression of the disease. The team, led by associate professor in Ohio State’s Department of Veterinary Biosciences Dr. Ian Davis, discovered this by determining all miR expression levels in ALI lung cells. The results showed that miR-155 was highly over-expressed by alveolar type II (ATII) cells , which are the primary site of influenza virus replication. As influenza increases in severity, miR-155 expression becomes greater. This is harmful because an upregulation of miR-155 seems to provoke a raise in several types of white blood cells and signaling proteins, causing lung inflammation.
Since miR-155 expression by ATII cells could be responsible for the progression of influenza-triggered ALI, Schermerhorn and Davis hypothesize that miR-155 may be a target for therapeutic intervention. Influenza-induced ALI becomes less severe in mice that ATII cell miR-155 expression has been blockaded, called miR-155-knockout mice.
This summer, Schermerhorn is testing a gene therapy method’s ability to delay onset or reduce severity of influenza-induced ALI in mice. The method involves inserting pieces of specially engineered DNA – in this case lipoplexes carrying antagomiRs – into mice that will target ATII cells and inhibit miR-155 expression. His results will give further data on the role of miR-155 in influenza development in general, as well as the efficacy of inhibiting ATII cell miR-155 expression with antagomiRs.
“Research in public health and infectious diseases has always interested me; I like to solve problems,” Schermerhorn said. “Since influenza is a high-consequence pathogen, this study was a good fit from the start.”