Comprehensive analysis of SARS‐CoV‐2 receptor proteins in human respiratory tissues identifies alveolar macrophages as potential virus entry site

Abstract

Comprehensive analysis of SARS-CoV-2 receptor proteins in human respiratory tissues identifies alveolar macrophages as potential virus entry site Aims: COVID-19 has had enormous consequences on global health-care and has resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, and alveolar macrophages were suggested as a potential viral entry cell type and vector for intra-alveolar virus transmission. Here, we investigated the protein expression of 10 well-known and novel virus entry molecules along potential entry sites in humans using immunohistochemistry. Methods and results: Samples of different anatomical sites from up to 93 patients were incorporated into tissue microarrays. Protein expression of ACE2, TMPRSS2, furin, CD147, C-type lectin receptors (CD169, CD209, CD299), neuropilin-1, ASGR1 and KREMEN1 were analysed. In lung tissues, at least one of the three receptors ACE2, ASGR1 or KRE-MEN1 was expressed in the majority of cases. Moreover, all the investigated molecules were found to be expressed in alveolar macrophages, and colocalisation with SARS-CoV-2 N-protein was demonstrated using dual immunohistochemistry in lung tissue from a COVID-19 autopsy. While CD169 and CD209 showed consistent protein expression in sinonasal, conjunctival and bronchiolar tissues, neuropilin-1 and ASGR1 were mostly absent, suggesting a minor relevance of these two molecules at these specific sites. Conclusion: Our results extend recent discoveries indicating a role for these molecules in virus entry at different anatomical sites. Moreover, they support the notion of alveolar macrophages being a potential entry cell for SARS-CoV-2.

Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease

“…Interestingly, Kringle containing transmembrane protein 1 (KREMEN1) is a transmembrane receptor involved in WNT signalling that has recently been proposed as an alternative receptor for the SARS-CoV-2 virus 22 . KREMEN1 is a known entry receptor for enteroviruses, such as coxsackievirus A10, and is expressed at potential virus entry sites (i.e., sinonasal, conjunctival and bronchiolar epithelium) 44,45 . In blood, KREMEN1 expression is mainly restricted to leucocytes, including neutrophils, monocytes, T cells and B cells.…”