Ephrin Receptors, Dysgeusia and COVID-19

 

         Dysgeusia or parageusia is a distortion of the sense of taste. It is often associated with ageusia the complete lack of taste or with hypogeusia, a decrease in taste sensitivity. New-onset dysgeusia is a potential early marker of COVID-19 infection. There are many important receptors that play a role in the mechanism of gustation. 

         In the article “Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory Papillae” by Treffy et al. studied the innervation of taste buds as a model for further looking into axon targeting mechanisms. Specifically they looked at Ephs and ephrins and their roles as receptors and or ligands in gustation because papilla epithelium have more cell-cell interactions and Ephs and ephrins are cell-attached proteins. This study focused on Ephrin-Bs specifically in taste axon targeting. Ephrin-Bs are transmembrane proteins that interact primarily with EphBs. The localization of ephrin-B2 and EphB1/EphB2 supported a role for forward ephrinB/EphB signaling with axon targeting on lingual epithelium. Stripe assays were used to determine whether ephrin-B1-Fc or ephrin-B2-Fc fusion proteins repelled or stabilized geniculate neurite outgrowth in vitro. Results showed that NT4-promoted neurite outgrowth from E15 and E18 geniculate ganglia was repelled by 40 μg/ml ephrin-B2 stripes, and that E18 neurites were repelled by 10 μg/ml ephrin-B2 stripes (fig. 4a, b, darker purple bars). Lam- inin also decreased the suppression of outgrowth by ephrin-Fc; at E15 and E18, regardless of whether BDNF or NT4 was used to promote outgrowth (Pg. 8-9). Lastly Treffy et. al looked to determine whether ephrin-B/EphB signaling has an impact on gustatory innervation in vivo by looking at the innervation of fungiform papillae without EphB1 and EphB2. The data was consistent with the idea that ephrin-B2/EphB signaling stabilizes axons during arborization within papillae. The data shows that ephrin-B/EphB signaling is enough to repress growth from gustatory neuritis in vitro and required for innervation of gustatory papillae in vivo. EphBs are expressed in sensory afferents at targeting stages, ephrin-B1 is expressed in pathway of gustatory axons and ephrin-B2 is expressed in papilla epithelium after initial target penetration. Conclusively, the results show that ephrin-B forward signaling is required for normal gustatory innervation of the tongue. 

         In the article “Dysgeusia in COVID-19: Possible Mechanisms and Implications” by Lozada-Nur et al. includes a summary of recent publications on epidemiological studies and reports with prevalence ranging from 71% to 88.8% for taste disturbances in patients with COVID-19. Taste disturbances included ageusia, hypogeusia and dysgeusia. The study explains that chemosensory dysfunction is a common occurrence with numerous medical conditions (e.g., upper respiratory viral infection; diabetes, heart disease; Alzheimer disease; asthma; liver and kidney diseases; chronic hepatitis C virus infection; hypothyroidism; Parkinson disease; or depression). Several medications are known to interfere with taste as well. The article brings up questions to be further looked into in regards to dysgeusia and COVID-19, asking if dysgeusia is a prognostic marker for the severity of COVID-19 or for progression to other disease manifestations and what are the mechanisms by which taste dysfunction develops in SARS-CoV-2 infection.

         The article talks about Angiotensin-converting enzyme 2 (ACE2) receptors found in the epithelium of taste buds and salivary glands. In papilla epithelium one can also find Ephs and ephrin receptors which play a role in normal gustatory innervation of the tongue.  These receptors are important in taste and taste, specifically the loss of taste plays an important role in recognizing COVID-19. Therefore better understanding of the mechanism of gustation as the first article aims to do could help with understanding taste disturbances associated with COVID-19 and other medical conditions as listed in the article. Both bring up a potential for further studies to look into in order to better understand the mechanisms behind dysgeusia and COVID-19 and the correlation between the two. 

 

Citations

 

Treffy, Randall William, et al. “Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory Papillae. Developmental Neuroscience, U.S. National Library of Medicine, 2 Apr. 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4927353/

 

Lozada-Nur, Francina, et al. Dysgeusia in COVID-19: Possible Mechanisms and Implications. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Published by Elsevier Inc., Sept. 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7320705/