Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections
© 2023. Springer Nature Limited..
Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades. Although several receptors and co-receptors have been reported for Ebola virus, key host factors remain to be elucidated. In this study, using a haploid cell screening platform, we identify the guanine nucleotide exchange factor CCZ1 as a key host factor in the early stage of filovirus replication. The critical role of CCZ1 for filovirus infections is validated in 3D primary human hepatocyte cultures and human blood-vessel organoids, both critical target sites for Ebola and Marburg virus tropism. Mechanistically, CCZ1 controls early to late endosomal trafficking of these viruses. In addition, we report that CCZ1 has a role in the endosomal trafficking of endocytosis-dependent SARS-CoV-2 infections, but not in infections by Lassa virus, which enters endo-lysosomal trafficking at the late endosome stage. Thus, we have identified an essential host pathway for filovirus infections in cell lines and engineered human target tissues. Inhibition of CCZ1 nearly completely abolishes Marburg and Ebola infections. Thus, targeting CCZ1 could potentially serve as a promising drug target for controlling infections caused by various viruses, such as SARS-CoV-2, Marburg, and Ebola.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Nature communications - 14(2023), 1 vom: 25. Okt., Seite 6785 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Monteil, Vanessa [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 13.11.2023 Date Revised 19.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-023-42526-6 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363724567 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363724567 | ||
| 003 | DE-627 | ||
| 005 | 20231226093947.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-023-42526-6 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1212.xml |
| 035 | |a (DE-627)NLM363724567 | ||
| 035 | |a (NLM)37880247 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Monteil, Vanessa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections |
| 264 | 1 | |c 2023 | |
| 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 13.11.2023 | ||
| 500 | |a Date Revised 19.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. Springer Nature Limited. | ||
| 520 | |a Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades. Although several receptors and co-receptors have been reported for Ebola virus, key host factors remain to be elucidated. In this study, using a haploid cell screening platform, we identify the guanine nucleotide exchange factor CCZ1 as a key host factor in the early stage of filovirus replication. The critical role of CCZ1 for filovirus infections is validated in 3D primary human hepatocyte cultures and human blood-vessel organoids, both critical target sites for Ebola and Marburg virus tropism. Mechanistically, CCZ1 controls early to late endosomal trafficking of these viruses. In addition, we report that CCZ1 has a role in the endosomal trafficking of endocytosis-dependent SARS-CoV-2 infections, but not in infections by Lassa virus, which enters endo-lysosomal trafficking at the late endosome stage. Thus, we have identified an essential host pathway for filovirus infections in cell lines and engineered human target tissues. Inhibition of CCZ1 nearly completely abolishes Marburg and Ebola infections. Thus, targeting CCZ1 could potentially serve as a promising drug target for controlling infections caused by various viruses, such as SARS-CoV-2, Marburg, and Ebola | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Vesicular Transport Proteins |2 NLM | |
| 700 | 1 | |a Kwon, Hyesoo |e verfasserin |4 aut | |
| 700 | 1 | |a John, Lijo |e verfasserin |4 aut | |
| 700 | 1 | |a Salata, Cristiano |e verfasserin |4 aut | |
| 700 | 1 | |a Jonsson, Gustav |e verfasserin |4 aut | |
| 700 | 1 | |a Vorrink, Sabine U |e verfasserin |4 aut | |
| 700 | 1 | |a Appelberg, Sofia |e verfasserin |4 aut | |
| 700 | 1 | |a Youhanna, Sonia |e verfasserin |4 aut | |
| 700 | 1 | |a Dyczynski, Matheus |e verfasserin |4 aut | |
| 700 | 1 | |a Leopoldi, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Leeb, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Volz, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Hagelkruys, Astrid |e verfasserin |4 aut | |
| 700 | 1 | |a Kellner, Max J |e verfasserin |4 aut | |
| 700 | 1 | |a Devignot, Stéphanie |e verfasserin |4 aut | |
| 700 | 1 | |a Michlits, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Foong-Sobis, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Friedemann |e verfasserin |4 aut | |
| 700 | 1 | |a Lauschke, Volker M |e verfasserin |4 aut | |
| 700 | 1 | |a Horn, Moritz |e verfasserin |4 aut | |
| 700 | 1 | |a Feldmann, Heinz |e verfasserin |4 aut | |
| 700 | 1 | |a Elling, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Penninger, Josef M |e verfasserin |4 aut | |
| 700 | 1 | |a Mirazimi, Ali |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 14(2023), 1 vom: 25. Okt., Seite 6785 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g number:1 |g day:25 |g month:10 |g pages:6785 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-023-42526-6 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |e 1 |b 25 |c 10 |h 6785 | ||