Friday, April 19, 2024
4/19/2024
PROJECT SUMMARY / ABSTRACT Taste deficits are prevalent in people infected with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic. The loss of taste sensation negatively affects nutrition and quality of life and in some patients this deficit is long-lasting. The biological basis for taste loss due to SARS-CoV-2 is largely unknown. Our preliminary results demonstrate that the ACE2 receptor and TMPRSS2 which together mediate SARS-CoV-2 host cell entry are expressed in taste buds indicating their potential for viral infection. The function of taste cell ACE2, also a member of the renin-angiotensin system that regulates fluid balance, is unknown. We have developed three novel genetic mouse strains to overcome the limitations of currently available mouse models. In aim 1 we map ACE2 reporter expression to determine which taste receptor cell populations and pathways are potential targets of SARS-CoV-2. In aim 2 we test how lingual epithelium-specific ACE2 contributes to taste receptor cell dynamics and neurophysiological taste responses under baseline and inflammatory conditions. We will also test how taste function is affected by human SARS-CoV-2 spike protein in a humanized ACE2 knock-in mouse. Our hypothesis predicts that taste buds are SARS-CoV-2 targets, that taste ACE2 contributes to taste function and is protective during inflammation, and that SARS-CoV-2 spike protein will exacerbate damage in taste buds and depress neural taste responses under inflammatory conditions. This R21 Exploratory / Developmental grant application addresses the urgent need for fundamental insights to mechanisms underlying taste dysregulation in people with COVID-19.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
