Ace2 in the healthy and inflamed taste system

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Lin  Gan
Organization: AUGUSTA UNIVERSITY
Fiscal Year: 2022
Award: $231,000
Funding agency: National Institute on Deafness and Other Communication Disorders

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.

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