Colorado State University Study Identifies Potential New Target for Antivirals

A Colorado State University study may have identified a new target to treat viral illnesses by manipulating the amount or availability of a protein in cells called HuR that regulates and stabilizes cell messages, such as those tied to immune system responses.

“There are 20 to 30 alphaviruses that have been described to date that cause a range of diseases from fevers to encephalitis” said Jeff Wilusz, a professor in the department of Microbiology, Immunology and Pathology. “We haven’t been very successful in finding treatments against many viruses, including the ones that have caused some of the most significant epidemics of mosquito-borne viral illnesses to date. If we can develop antivirals that block alphaviruses from interacting with the HuR protein, we may be able to treat viral infections much more effectively than we can today.”

In normal cell functions, a protein called HuR regulates cellular messages and gene expression within the cell by binding to cellular RNA. Its job is to prevent the degradation of select RNAs so that genes can get turned on to do their work, such as launching an immune system response against an attacking virus.

The decay of RNA is a natural, important cellular process that also plays a role in policing gene expression in the cell, efficiently removing unwanted or defective RNAs. Viruses also have RNA but viral RNA is unwanted inside the cell because it is harmful. For viruses to reproduce in a cell, viral RNA must figure out a way to avoid getting degraded. Until now scientists knew very little on how the RNA of viruses avoided the cellular RNA degradation machinery. This study shows that a large family of viruses steals HuR proteins, causing the cellular protein to bind to the viral RNAs instead of a cellular RNA. Without the HuR protein, key cellular RNAs likely become unstable and can’t efficiently decode the message for an immune response; the virus may also block or reduce regular cellular immune responses. Without the immune response, the virus multiplies very effectively.

In the study, CSU researchers led by Wilusz, lowered the amount of HuR protein in the cell and found that it caused RNAs made by alphaviruses, a family of viruses that are mostly spread by mosquitoes, to be very unstable and that the viral infection was then more easily controlled because the virus couldn’t reproduce as easily when it could not bind with the HuR protein.

The question of how a virus interacts with the RNA decay machinery inside a cell has not been closely researched in the past. The role of RNA decay in the cell also has been an area that has not received much attention by researchers, and only in the past 10 years have extensive efforts been made to better understand those important functions.

The CSU study was published this week in Cell Host and Microbe.