Tracking the virus that causes COVID-19 as it moves through animals and humans has been very difficult for scientists combating the coronavirus pandemic — until now.
A team of researchers at Texas Biomedical Research Institute has discovered a way to insert a tracker, called a reporter gene, into the SARS-CoV-2 virus. The gene causes the virus to glow brightly under a fluorescence microscope, allowing scientists to see how the virus moves through its host in real time.
The significance of this is immense, said Luis Martinez-Sobrido, a virologist and the lead researcher of the project at the San Antonio-based institute.
“These glowing viruses allow us to track what cells are infected, either in the laboratory in a petri dish, or where the virus goes in animal models,” he said. “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 antiviral drugs and vaccines.”
The modified viruses also give scientists an idea of the viral load — the amount of virus in an infected host — within a person or animal, which can affect how quickly the body can combat and overcome the virus.
Being able to physically view the virus’s location in its host and to observe the viral load offers scientists many advantages over other techniques, said molecular biologist Chengjin Ye, a member of Martinez-Sobrido’s research team.
“Instead of needing a large team to screen 2,000 compounds to see if they work against the virus, one person could do that with a reporter virus in a few hours,” Ye said.
It also allows researchers to watch the virus as it travels through an animal, rather than requiring multiple animals to gain the same insights.
In recent weeks, Martinez-Sobrido and his team have shared their modified SARS-CoV-2 viruses and its plasmids — a type of genetic structure in a cell — with more than 100 qualified labs around the world. This will significantly help scientists in the fight against COVID-19, said Cory Hallam, Texas Biomed’s vice president of innovation management.
“This is science in real time,” Hallam said.
Texas Biomed researchers have been working to create the luminous SARS-CoV-2 viruses since Martinez-Sobrido joined the institute’s staff in February, the researcher said.
To create the glowing viruses, Martinez-Sobrido and his team performed several advanced biological processes to add the bioluminescent reporter gene into SARS-CoV-2’s genetic sequence. As these modified viruses replicate, their progeny also have the inserted gene in their genetic code.
Martinez-Sobrido and his team’s early attempts were insufficient; the team placed the reporter gene into a section of the virus’s genetic code that resulted in a faint, dimly glowing virus that was difficult to see.
To turn up the brightness, the researchers inserted the reporter gene into a different part of the virus’ genetic code that would result in the production of more glowing proteins.
This time, the glow was so bright, “it almost blinded me when I looked through the fluorescent microscope,” Ye said.
The researchers were able to prove the modified virus also behaves like the normal SARS-CoV-2 virus, which is important because it tells scientists how SARS-CoV-2 acts outside the lab.
The SARS-CoV-2 virus is a tricky virus to modify, making this science very important, said Adolfo García-Sastre, a professor in the department of microbiology and director of the Global Health and Emerging Pathogens Institute of Icahn School of Medicine at Mount Sinai in New York, whose 25-plus years of research has focused on the molecular biology of influenza viruses and several other RNA viruses.
To successfully modify the virus without changing its behavior can take a lot of time, effort, and strategies, García-Sastre said.
“You’d need to find a place where the gene is sustainable, so it’s not a given that is easy to make,” he said. “This is a great job on their account.”