Scientists reveal way deadly virus hijacks cells – and a way to stop it
Respiratory syncytial virus (RSV) is responsible for an estimated 200,000 deaths worldwide a year, exceeding the toll of influenza. There are no effective anti-RSV therapeutics generally available and no vaccine.
Monash Biomedicine Discovery Institute (BDI) researchers have discovered that a drug being trialled clinically for other diseases may potentially treat RSV, also called pneumovirus. Moreover, Dr MengJie Hu and her supervisor Professor David Jans, found a key mechanism in the way the virus attacks host cells, opening the possibility of developing more treatments.
Their study, published in eLife, found that mitochondria – the cell’s energy generator – was corrupted by the virus, which then used it to its own ends.
Dr Hu used sophisticated dyes and quantitative imaging technologies to reveal the interface between the virus and mitochondria.
“What MengJie has done for the first time is delineate what happens to a cell infected by RSV in terms of the mitochondria being moved around and ‘switched off’,” Professor Jans said.
“What happens then is that instead of energy generation, the mitochondria start making reactive oxygen species for a transient time, which helps the virus,” he said.
Reactive oxygen species (ROS) are created as a natural byproduct of the metabolism of oxygen but can damage cells at excessive levels.
Dr Hu tested various drugs targeting the RSV-host cell mitochondrial interface, and found that a mitochondrial selective anti-oxidant, MitoQ, stopped the virus in cell cultures, in animal models, and in human samples.
“This makes MitoQ a really exciting treatment option,” Professor Jans said.
MitoQ is being trialled for cardiovascular, Parkinson’s and Hepatitis C virus infection diseases where there is ROS damage, and has been proved to be safe, Dr Hu said.
“I think with the information from our study, this will help us develop the right weapon against RSV,” she said.
“Despite decades of research and lots of money and effort in RSV research, we have no vaccine and no usable, generally available anti-viral treatment either, so the discovery by MengJie is a huge step forward,” said study co-author Professor Reena Ghildyal, respiratory virus expert from the University of Canberra.
“We now have the opportunity to repurpose drugs,” she said.
This would dramatically reduce the time to a new RSV treatment becoming available for high-risk adult patients – the elderly and people who are immunosuppressed –and young infants, particularly those born prematurely, who are prone to the disease.
Monash University provided strategic seed funding for the project, which also involved researchers from the University of Melbourne, University of Canberra, University of Newcastle and the Baker Heart and Diabetes Institute.
Read the full paper in eLife titled Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production.
Watch this animation to better understand the approach taken by Dr MengJie Hu, a member of Professor David Jans' research team.
About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.