COVID-19: Investigation of temporal innate immune responses induced by COVID-19 Spike Protein in primary murine Bone Marrow-Derived Macrophages.
EMSL Project ID
51597
Abstract
Circadian rhythms are roughly 24-hour cycles in the biochemical, physiological or behavioral processes of living entities. They are highly conserved and adjust innumerable actions affecting everything from luminescence in bacteria to sleep in humans. Disruptions in the clock negatively impact the human long-term medical outlook, notably increasing the risk for inflammation and viral-infection susceptibility. Circadian rhythms are controlled via a highly regulated transcription-translation based negative feedback loop that can modulate a large portion of the molecular output of the cell. Through the ideal programming of behavior, the clock enhances fitness by ensuring that many organismal functions are optimally timed with the phase of the circadian day.An example of the importance of the circadian clock is the anticipation of the time of day in conjunction with the mammalian immune response; many components of the immune system are believed to be under circadian control. This regulation is significant, as disruptions in circadian rhythms can lead to increased rates of inflammation, the result of a misregulated immune system. Moreover, temporal changes in the response to immune challenges, including viral infections and inflammation, have been noted. As the over-activation of the immune system is a common feature of the novel SARS-like pneumonia caused by COVID-19 and correlates with poor prognosis and health outcomes, time-of-day may have a significant effect on the immune response to COVID-19. Moreover, our work tracking the transcriptome and proteome over circadian time in murine bone-marrow derived macrophages demonstrates that angiotensin-converting enzyme 2 (ACE2), the receptor by which the spike (S) protein of coronavirus facilitates viral entry into target cells, oscillates in a circadian manner. We therefore hypothesize that the cellular response to COVID-19 is dependent upon the time of day in which the patient is exposed to the virus.
Project Details
Project type
Limited Scope
Start Date
2020-09-01
End Date
2022-06-30
Status
Closed
Released Data Link
Team
Principal Investigator