Co-expression of peripheral olfactory receptors with SARS-CoV-2 infection mediators: Potential implications beyond loss of smell as a COVID-19 symptom

Rachel Kerslake, Marcia Hall, Harpal S. Randeva, Demetrios A. Spandidos, Kamaljit Chatha, Ioannis Kyrou, Emmanouil Karteris*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) enters into human host cells via mechanisms facilitated mostly by angiotensin.converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). New loss of smell (anosmia/hyposmia) is now recognized as a COVID-19 related symptom, which may be caused by SARS-CoV-2 infection and damage of the olfactory receptor (OR) cells in the nasal neuro.epithelium and/or central involvement of the olfactory bulb. ORs are also expressed peripherally (e.g., in tissues of the gastrointestinal and respiratory systems) and it is possible that their local functions could also be impaired by SARS-CoV-2 infection of these tissues. Using Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas, Genotype.Tissue Expression, cBioPortal and Shiny Methylation Analysis Resource Tool, we highlight the expression of peripheral ORs in both healthy and malignant tissues, and describe their co.expression with key mediators of SARS-CoV-2 infection, such as ACE2 and TMPRSS2, as well as cathepsin L (CTSL; another cellular protease mediating SARS-CoV-2 infection of host cells). A wide expression profile of peripheral ORs was noted, particularly in tissues such as the prostate, testis, thyroid, brain, liver, kidney and bladder, as well as tissues with known involvement in cardio.metabolic disease (e.g., the adipose tissue, pancreas and heart). Among these, OR51E2, in particular, was significantly upregulated in prostate adenocarcinoma (PRAD) and co.expressed primarily with TMPRSS2. Functional networks of this OR were further analysed using the GeneMANIA interactive tool, showing that OR51E2 interacts with a plethora of genes related to the prostate. Further in vitro and clinical studies are clearly required to elucidate the role of ORs, both at the olfactory level and the periphery, in the context of COVID-19.

Original languageEnglish
Pages (from-to)949-956
Number of pages8
JournalInternational Journal of Molecular Medicine
Volume46
Issue number3
Early online date17 Jun 2020
DOIs
Publication statusPublished - 1 Sep 2020

Bibliographical note

© Kerslake et al. This work is licensed under a Creative Commons
Attribution-NonCommercial-NoDerivatives 4.0
International (CC BY-NC-ND 4.0) License

Keywords

  • Angiotensin-converting enzyme 2
  • Anosmia
  • Cathepsin L
  • COVID-19
  • DNA methylation
  • Olfactory receptors
  • Pan-cancer
  • Prostate cancer
  • SARS-CoV-2
  • Transmembrane protease serine 2

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