The Heather Christofk laboratory in the UCLA Department of Biological Chemistry is studying how viruses reprogram metabolism of host cells to promote viral replication. Viruses take over host cell metabolism through specific flux-altering enzymes, enhancing glycolysis and anabolism to meet the bioenergetics and biosynthetic demands of viral replication. Defining the mechanistic events necessary for virus-induced metabolic changes and mapping the impact of they have on anabolic metabolism and virus infection, will further elucidate viral disease pathology. Researchers have recently identified that adenovirus, vesicular stomatitis virus, and influenza A virus infections down-regulate the nutrient sensing arm of the mTORC1 pathway to enable mTORC1 activation and macromolecule synthesis, even as intracellular nutrient pools become scarce. Dr. Chirstofk and colleagues hypothesize that COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, may act by a similar mechanism to hijack host cell metabolic processes.
Scientists from the Chirstofk laboratory have teamed up with Dr. Arumugaswami and coworkers to model SARS-CoV-2 infection in VERO cells. Preliminary results indicate that this virus behaves similarly to the aforementioned adenovirus, vesicular stomatitis virus, and influenza A, to manipulate the mTORC1 pathway to promote viral infection. Future work seeks to utilize COVID-19 patient lung tissue samples to investigate whether mTORC1 is activated as expected and evaluate the down-regulation of nutrient sensing pathway components. This research provides translationally relevant insights of SARS-CoV-2 viral infection metabolic mechanisms that may serve as crucial therapeutic targets.
Link to Faculty Webpage: https://www.christofklab.com/
Relevant Cases:
1) Viral hijacking of cellular metabolism. BMC Biology (2019)