Autophagy and Mitophagy-Related Pathways at the Crossroads of Genetic Pathways Involved in Familial Sarcoidosis and Host-Pathogen Interactions Induced by Coronaviruses
Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Cells - 10(2021), 8 vom: 05. Aug. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pacheco, Yves [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.09.2021 Date Revised 07.12.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/cells10081995 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM329836749 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM329836749 | ||
| 003 | DE-627 | ||
| 005 | 20231225210002.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cells10081995 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1099.xml |
| 035 | |a (DE-627)NLM329836749 | ||
| 035 | |a (NLM)34440765 | ||
| 035 | |a (PII)1995 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pacheco, Yves |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Autophagy and Mitophagy-Related Pathways at the Crossroads of Genetic Pathways Involved in Familial Sarcoidosis and Host-Pathogen Interactions Induced by Coronaviruses |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.09.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV2 | |
| 650 | 4 | |a TANK Binding Kinase 1 | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a mitophagy | |
| 650 | 4 | |a sarcoidosis | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a TBK1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Valeyre, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a El Jammal, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Vallee, Maxime |e verfasserin |4 aut | |
| 700 | 1 | |a Chevalier, Fabien |e verfasserin |4 aut | |
| 700 | 1 | |a Lamartine, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Sigaudo-Roussel, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Verrier, Bernard |e verfasserin |4 aut | |
| 700 | 1 | |a Israel-Biet, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Freymond, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Cottin, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Calender, Alain |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cells |d 2011 |g 10(2021), 8 vom: 05. Aug. |w (DE-627)NLM227066421 |x 2073-4409 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:8 |g day:05 |g month:08 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cells10081995 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 8 |b 05 |c 08 | ||