A Proofreading Virus: Mark Denison Discusses his Coronavirus Research

Researcher Mark Denison has studied infectious diseases and specifically coronaviruses for decades and he explains some unique elements of their daunting mechanisms. He discusses

• What's different about their genome size, replicating capabilities, protein encyclopedia, and more;
• How the enzyme that provides its proofreading system is a standalone in RNA viruses and why that's important to its function; and
• How all these variables are working toward different theories about ways to manage its infiltration.

Mark Denison is Director of the Division of Pediatric Infectious Diseases at Vanderbilt University. He's spent much of his career working with coronaviruses and was concerned about a scenario like our current one long before March. He backs up and explains some general findings about coronaviruses including their unique capacity for rapid evolution and adaptation, entry, recruitment of cellular machinery, and so on. He tells listeners that they have significantly more base pairs than other RNA viruses. In fact, this is one of the largest RNA replicating genomes known. Its mechanisms are responsible for symptoms like recurrent fever causes and vulnerability for immunodeficiency sufferers.

In 2007, Dr Denison and his team made a significant discovery about this type of virus after years of mystification surrounding its ability to regulate itself, as if it were not error prone, unlike other RNA viruses. They found that coronaviruses are the only known organisms that encode an RNA-dependent, RNA-proofreading system. Many organisms have a proofreading system for copying, but most RNA viruses, like dengue for example, lack the ability to fix mistakes. They create a crowd of mutants around them. Denison explains how this determines the ecology of most RNA viruses and how the enzyme that proofreads for coronaviruses makes for a very different ecology and virulence quality. He also explains the experiments his lab has made on the SARS-CoV-2 "wild-type" virus they've worked with to either decrease or increase its mutation rates as well as connections with therapy possibilities. He addresses concerns about flu season and the difficulty in diagnosing recurrent fever causes when both are an issue. Finally, he offers a reality check on what we can predict about SARS-CoV-2's future in the general population and those with immunodeficiency.

For more, google his name and see his lab website: www.vumc.org/denison-lab. Available on Apple Podcasts: apple.co/2Os0myK