Queensland study may fast-track understanding of Zika virus

Scientists looking at the genetics of Zika virus have used a new technique that allows scientists to massively speed up evolution in the test tube in order to understand viral evolution in nature.

The study, led by The University of Queensland and QIMR Berghofer Medical Research Institute, used deep mutational scanning to analyse the thousands of different ways Zika virus can mutate.

Professor Andreas Suhrbier, who heads QIMR Berghofer’s Inflammation Biology laboratory, said viruses mutated all the time all around us and while most of those mutations had little consequence for humanity, some could cause outbreaks of human disease.

“What mutations are boring? What mutations are important for increasing virus transmission by mosquitoes? What mutations cause serious health issues?  These are not simple questions to answer, but our paper illustrates how this new technology can provide insights” Professor Suhrbier said.

“We usually see a disease outbreak and then try and work out what mutations might have caused the outbreak.  This new technique allows us to look at all possible mutations at once, rather than waiting for nature to generate mutations in the course of years of evolution.

“The ultimate goal for this kind of technology, which is currently in its infancy, is to know what a dangerous mutation looks like, allowing us to be forewarned when it turns up on our doorstep.

“A similar strategy is used for influenza and is highly effective, but up till now we have had no method by which we can start to do the same thing for mosquito-borne diseases like Zika.”

Dr Yin Xiang Setoh from UQ’s School of Chemistry and Molecular Biosciences said the technique would supercharge research on Zika virus and speed up our understanding of virus evolution.

“Viruses like Zika have to replicate in both mosquitoes and in mammals such as humans” he said.

“We used deep mutational scanning to learn that two mutations are in fact important for efficient growth in mosquitoes.  Critically, these mutations significantly reduced replication in human cells.

“So in this first proof-of-concept study, we have identified two mutations that are great for replication in mosquitoes, but are unlikely to be the cause of a major human outbreak.  Two down, thousands more to investigate!”

Associate Professor Alexander Khromykh, who heads RNA Virology laboratory at UQ, said the technology was an exciting development that promised to fast-track understanding of viral evolution.

“Using this rapid technique, our next goal is to identify mutations that promote the ability of Zika virus to cross the placenta and enter and infect the foetal brain,” he said.

“This technology can also be applied to investigate the development of the disease and the transmission of a range of similar viruses, transmitted by mosquitoes, ticks and other invertebrates.

“It took us a number of years, not to mention a significant collaborative effort, to get to this stage and we’re incredibly excited to see what’s next.”

The study was initiated with seed funding from the Australian Infectious Diseases Research Centre.

It has been published in the journal Nature Microbiology