Presentation Details
| Persistent severe acute respiratory syndrome coronavirus 2 infection and taste nerve degeneration driven by impaired interferon regulatory factor 3 signaling Kang-Hoon Kim1, Emma Larsson1, Janna Oh1, Heaven Branch1, Peihua Jiang1, Danielle R.Reed1, Richard Bowen2, Hong Wang1. 1Monell Chemical Senses Center, Philadelphia, PA, USA.2Colorado State University, Fort Collins, CO, USA |
Abstract
Taste loss is prevalent with SARS-CoV-2 infection. While taste function restored quickly in many patients, some experienced sustained taste loss lasting more than several months. To study the underlying mechanism of taste loss, we used transgenic mouse models that express the human angiotensin-converting enzyme 2 (hACE2), the receptor for SARS-CoV-2 in humans. We used SARS-CoV-2 susceptible hACE2 knock-in and mACE2 knockout mice. Our results show that taste tissues can be infected by SARS-CoV-2, and both viral RNAs and proteins can be detected. Antibody staining experiments show that SARS-CoV-2 can infect types II and III taste bud cells that are responsible for sensing sweet, umami, bitter, and sour tastes. In addition, we generated mouse strains that express hACE2 but lack the antiviral gene, interferon regulatory factor 3 (IRF3) or type I interferon receptor 1 (IFNAR1). Recent studies have shown that inborn genetic errors in key antiviral genes are present in human populations and are enriched in patients with severe COVID-19. Thus, the double-transgenic mouse strains allow us to investigate whether deficiencies in antiviral genes contribute to SARS-CoV-2-induced taste loss. We found that taste tissues of IRF3-knockout mice contained detectable SARS-CoV-2 RNAs at 36 days post infection (5.4-fold, p=0.008), while viral RNAs were cleared from taste tissues of mice with functional IRF3. Furthermore, we observed a significant reduction of taste nerve fibers within taste buds at 7 and 36 dpi in IRF3-knockout mice. Diminished taste nerve innervation may arise, in part, due to SARS-CoV-2–induced complements that promote synaptic elimination in taste buds. This suggests a mechanistic link between IRF3 deficiency and the pathological impairments underlying long-term post-viral taste loss.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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