Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses
Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. Howe...
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| Format: | Article |
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MDPI AG
2019-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/7/1636 |
| _version_ | 1811283253941764096 |
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| author | Tanja Becker Vu Thuy Khanh Le-Trilling Mirko Trilling |
| author_facet | Tanja Becker Vu Thuy Khanh Le-Trilling Mirko Trilling |
| author_sort | Tanja Becker |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV. |
| first_indexed | 2024-04-13T02:08:10Z |
| format | Article |
| id | doaj.art-55e7517629104a66a620a2885172b266 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T02:08:10Z |
| publishDate | 2019-04-01 |
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| spelling | doaj.art-55e7517629104a66a620a2885172b2662022-12-22T03:07:22ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01207163610.3390/ijms20071636ijms20071636Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of CytomegalovirusesTanja Becker0Vu Thuy Khanh Le-Trilling1Mirko Trilling2Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyHuman cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV.https://www.mdpi.com/1422-0067/20/7/1636human cytomegalovirusMLN4924DDB1Cullin RING ubiquitin ligasesantiviral drugs |
| spellingShingle | Tanja Becker Vu Thuy Khanh Le-Trilling Mirko Trilling Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses International Journal of Molecular Sciences human cytomegalovirus MLN4924 DDB1 Cullin RING ubiquitin ligases antiviral drugs |
| title | Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses |
| title_full | Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses |
| title_fullStr | Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses |
| title_full_unstemmed | Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses |
| title_short | Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses |
| title_sort | cellular cullin ring ubiquitin ligases druggable host dependency factors of cytomegaloviruses |
| topic | human cytomegalovirus MLN4924 DDB1 Cullin RING ubiquitin ligases antiviral drugs |
| url | https://www.mdpi.com/1422-0067/20/7/1636 |
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