BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.
- MeSH
- angiotensin konvertující enzym 2 genetika imunologie MeSH
- basigin genetika imunologie MeSH
- bronchiální astma epidemiologie genetika imunologie MeSH
- chronická nemoc epidemiologie MeSH
- chronická obstrukční plicní nemoc epidemiologie genetika imunologie MeSH
- COVID-19 epidemiologie genetika imunologie MeSH
- dipeptidylpeptidasa 4 genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu genetika MeSH
- hypertenze epidemiologie genetika imunologie MeSH
- kojenec MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obezita epidemiologie genetika imunologie MeSH
- předškolní dítě MeSH
- přirozená imunita imunologie MeSH
- rizikové faktory MeSH
- SARS-CoV-2 genetika imunologie MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Because free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity-related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced 11 candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena. Suitable single nucleotide polymorphism markers of potential functional importance, located in genes coding for basigin (BSG, CD147), the signaling lymphocyte activating molecule (SLAMF1), the poliovirus-related receptor-4 (NECTIN4, PVRL4), toll-like receptors 3, 7, 8 (TLR3, TLR7, TLR8), natural resistance-associated macrophage protein (SLC11A1) and natural cytotoxicity triggering receptor 1 (NCR1), were identified in each model species, along with MHC-DQB haplotypes unique for each species. This set of molecular markers represents a potentially useful tool for studying host genetic variation and susceptibility to morbillivirus infection in Cetaceans as well as for studying functionally important genetic diversity of selected Cetacean populations.
- MeSH
- basigin genetika imunologie MeSH
- biologické markery metabolismus MeSH
- delfíni rodu Stenella genetika imunologie virologie MeSH
- exprese genu MeSH
- genetická predispozice k nemoci * MeSH
- histokompatibilita - antigeny třídy II genetika imunologie MeSH
- infekce viry z rodu Morbillivirus genetika imunologie virologie MeSH
- jednonukleotidový polymorfismus * MeSH
- molekuly buněčné adheze genetika imunologie MeSH
- Morbillivirus imunologie patogenita MeSH
- Phocoena genetika imunologie virologie MeSH
- proteiny přenášející kationty genetika imunologie MeSH
- receptor 1 spouštějící přirozenou cytotoxicitu genetika imunologie MeSH
- SLAMF1 protein genetika imunologie MeSH
- toll-like receptor 3 genetika imunologie MeSH
- toll-like receptor 7 genetika imunologie MeSH
- toll-like receptor 8 genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH