According to a study published in the Journal of Biological Chemistry, researchers at Northwestern University have identified one of the ways the influenza virus disarms our natural defense system.

The virus decreases the production of key immune system-regulating proteins in human cells that help attack the invader. In order to do this, the virus switches on the microRNAs that regulate these proteins.

The study, conducted by molecular biologist Curt M. Horvath, is one of the first to demonstrate that the virus can alter the expression of microRNA to control immune responses in human lung cells.

The researchers found a new way that the virus and its host interact. By understanding how viruses trigger the immune system to attack the body, scientists will be able to develop new therapies to preserve the immune response and keep people healthy.

Horvath explained:

“It’s a battle of supremacy between virus and host. Our goal is to understand how the flu replicates in the host. Now we’ve discovered a new pathway in which the flu controls the immune response, by shutting down vital protein production. With better understanding of this mechanism, one day we may be able to customize therapeutics to target individual flu strains.”

Horvath is a professor of microbiology-immunology and medicine at the Feinberg School of Medicine. In addition, he is the Soretta and Henry Shapiro Research Professor in Molecular Biology and professor of molecular biosciences in the Weinberg College of Arts and Sciences.

A microRNA had only 17 to 24 nucleotides, and its function is to hinder or prevent the production of proteins in the body.

For several years, researchers have known that when a virus, such as influenza infects respiratory cells there is an immediate antiviral response at the cellular level — the first barrier for protecting the body from the virus. The majority of alterations that take place are due to antiviral gene expression.

Researchers first learned about small RNA pathways called microRNAs, which regulate gene expression, around 10 years ago. After this finding, Horvath set out to investigate the role of microRNAs in influenza virus infection and determine what they are contributing to the antiviral response.

In this study, the team set out to determine which microRNAs were activated in response to influenza A virus by examining human lung cells infected with the virus. The researchers focused on 6 microRNAS that were found to substantially increase during flu infections.

They discovered that the virus stimulated 2 microRNAs that switched on the genes IRAK1 and MAPK3. This resulted in a decrease in the amount of proteins that help switch on the immune response.

The virus uses the cell mechanisms to its advantage by switching off parts of the natural antiviral system. The flu takes over the expression of microRNAs for its own purposes. The flu increases the expression of microRNA, which lowers the amount of protein and diminishes the immune response.

The next step for Horvath is to look at the clinical outcomes. He is currently working alongside Pedro C. Avila, M.D., professor of medicine-allergy-immunology at the Feinberg School in order to determine if the microRNAS are disregulated in individuals with flu.

Written by Grace Rattue