New “reporter viruses” developed by Texas Biomed researchers make it much easier to observe and its variants in cells and live animals in the lab, and enables faster screening of potential anti-viral drugs, vaccines, and neutralizing antibodies.
A version of SARS-CoV-2, the virus that causes disease, has been successfully modified to glow brightly in cells and animal tissues, providing a real-time way to track the spread and intensity of viral infection as it happens in animal models, researchers at Texas Biomedical Research Institute (Texas Biomed) report in the journal The Proceedings of the National Academy of Sciences (PNAS).
“Now we can track where the virus goes in animal models for COVID-19,” said virologist Luis Martinez-Sobrido, Ph.D., a Professor at Texas Biomed, and senior paper author. “Being able to see how the virus progresses, and which organs and cell types it specifically targets, will be a big help for understanding the virus and optimizing anti-viral drugs and vaccines.”
In addition to tracking the virus, Martinez-Sobrido and his collaborators have already begun using the reporter viruses to screen how well neutralizing antibodies work against different variants of concern, as recently reported in the Journal of Virology.
To make the reporter virus, Martinez-Sobrido and his team combined several advanced molecular biology tools to add the genetic sequence for the fluorescent or bioluminescent “reporter” proteins to the virus genetic code. As the virus’s code is replicated and transcribed, so too is the code for the glowing proteins.
In an earlier study, the team replaced one of the virus’s genes with the gene for the glowing proteins, but this resulted in a very dim signal – the gene was not expressed enough to be easily detected in animals. To turn up the brightness, the researchers had to figure out how to get the virus to produce larger quantities of the reporter proteins.
Their solution: they inserted the reporter gene next to a different gene in SARS-CoV-2, specifically, the gene coding for the nucleocapsid protein. “It’s the most expressed protein in SARS-CoV-2,” said molecular biologist Chengjin Ye, Ph.D., a member of Martinez-Sobrido’s lab. This time, the signal was so bright, “it almost blinded me when I looked through the fluorescent microscope,” he said.
The reporter proteins work in cells and live animal models, in combination with imaging systems that detect the wavelengths of light emitted by the proteins. Being able to observe viral load and location visually offers many advantages over… Brinkwire News Summary.