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09 Jun 2021

A vital tool to study virus evolution in the test tube

Variants of viruses such as that causing COVID-19 can now be quickly studied in the laboratory, even before they emerge in nature and become a major public health challenge.

The University of Queensland, QIMR Berghofer Medical Research Institute, The Peter Doherty Institute for Infection and Immunity (Doherty Institute), Monash University, and Queensland Health have developed a technology to manipulate viruses synthetically allowing rapid analysis and mapping of new potential virus variants.

UQ Professor Alexander Khromykh said the technology was ideal for use during a global pandemic such as COVID-19.

“This technique gives us the ability to answer questions about whether the use of a particular drug or vaccine will lead to new coronavirus variants before those variants emerge in nature,” Professor Khromykh said.

“Up until now, we’ve mostly just waited and reacted to viral variants as they emerge, and in the case of SARS-CoV-2 the world has been hit by Indian, UK and South African variants*, just to name a few.

“Now we can mimic the massive ‘experiment’ going on in nature – where these mutations pop up due to natural selection – but we can do it safely in a strictly controlled and highly regulated biosecurity laboratory environment.”

The UQ-developed process uses copies of fragments from the viral genetic material to assemble the functional viral genome in a test tube.

This allows scientists to rapidly generate virus variants and assess their potential to evade antiviral treatments and vaccine-induced immunity.

University of Melbourne Professor Jason Mackenzie, Laboratory Head at the Doherty Institute said that by using this technology it is now possible to isolate human viruses directly from clinically relevant samples.

“Using this approach, my PhD student Joshua Deerain was able to generate and cultivate a circulating human norovirus directly from a patients’ sample supplied by the Victorian Infectious Diseases Reference Laboratory (VIDRL),” Professor Mackenzie said.

“Noroviruses are basically impossible to grow in the lab, so this provided us with a very fast and effective means of isolating the virus.

“Having this ability now allows us to isolate a range of other clinical viruses that have been difficult to grow in the lab and to investigate pathogenic determinants and accelerate vaccine design to currently unpreventable infectious diseases.”

QIMR Berghofer helped to evaluate infection and disease caused by the ‘test tube’-made virus in a mouse model to ensure the technology was able to generate authentic viruses.

Professor Andreas Suhrbier from QIMR Berghofer said the research was essential, as viruses were changing all the time.

“We can now monitor changes in viruses like SARS-CoV-2 and see what could escape from vaccines and anti-viral treatments.

“We can also investigate whether escape variants are more or less virulent in a mouse model and find out whether there are interventions from which the virus cannot escape.

“It’s great to finally have this vital tool and start tackling these challenging questions.”

The research has been published in Nature Communications (DOI: 10.1038/s41467-021-23779-5).

*WHO has now re-classified these variants as Alpha (UK), Beta (South African) and Delta (Indian).

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