Open AccessSystematic Investigation of SARS-CoV-2 Receptor Protein Distribution along Viral Entry Routes in Humans
Author(s) -
Konstantin Bräutigam,
Stefan Reinhard,
José A. Galván,
Martin Wartenberg,
Ekkehard Hewer,
Christian M. Schürch
Publication year - 2022
Publication title -
respiration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.264
H-Index - 81
eISSN - 1423-0356
pISSN - 0025-7931
DOI - 10.1159/000521317
Subject(s) - furin , tmprss2 , respiratory tract , lung , receptor , coronavirus , serine protease , viral entry , immunohistochemistry , transmembrane protein , proteases , ards , pathology , medicine , respiratory system , biology , microbiology and biotechnology , virology , protease , virus , viral replication , covid-19 , enzyme , anatomy , biochemistry , disease , infectious disease (medical specialty)
Background: The novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the human body via mucosal surfaces of the upper and/or lower respiratory tract. Viral entry into epithelial cells is mediated via angiotensin-converting enzyme 2 (ACE2) and auxiliary molecules, but the precise anatomic site of infection still remains unclear. Methods: Here, we systematically investigated the main SARS-CoV-2 receptor proteins ACE2 and transmembrane serine protease 2 (TMPRSS2), as well as 2 molecules potentially involved in viral entry, furin and CD147, in formalin-fixed, paraffin-embedded human tissues. Tissue microarrays incorporating a total of 879 tissue cores from conjunctival (n = 84), sinonasal (n = 95), and lung (bronchiolar/alveolar; n = 96) specimens were investigated for protein expression by immunohistochemistry. Results: ACE2 and TMPRSS2 were expressed in ciliated epithelial cells of the conjunctivae and sinonasal tissues, with highest expression levels observed in the apical cilia. In contrast, in the lung, the expression of those molecules in bronchiolar and alveolar epithelial cells was much rarer and only very focal when present. Furin and CD147 were more uniformly expressed in all tissues analyzed, including the lung. Interestingly, alveolar macrophages consistently expressed high levels of all 4 molecules investigated. Conclusions: Our study confirms and extends previous findings and contributes to a better understanding of potential SARS-CoV-2 infection sites along the human respiratory tract.