Herpesvirus infections, such as those induced by human cytomegalovirus (HCMV), induce specific DNA damages. DNA damages can lead to cell mutation, death, apoptosis and immune system activation. Various types of DNA damage are repaired through multiple repair pathways, such as base excision, nucleotide excision, homologous recombination and nonhomologous end joining. Changes in the activity of DNA repair proteins during viral infection can cause disturbances in the DNA repair system and change its mechanisms. This report reviews results from studies, assaying a DNA repair system in HCMV infection.

• MeSH
• cytomegalovirové infekce enzymologie   genetika   metabolismus   mikrobiologie   MeSH
• Cytomegalovirus fyziologie   MeSH
• enzymy opravy DNA genetika   metabolismus   MeSH
• lidé MeSH
• oprava DNA * MeSH
• poškození DNA MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed that helicase-like transcription factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses.

• MeSH
• cytomegalovirové infekce genetika   imunologie   virologie   MeSH
• Cytomegalovirus genetika   imunologie   fyziologie   MeSH
• DNA vazebné proteiny chemie   genetika   imunologie   MeSH
• imunitní únik MeSH
• lidé MeSH
• proteiny chemie   genetika   imunologie   MeSH
• proteomika MeSH
• stabilita proteinů MeSH
• transkripční faktory chemie   genetika   imunologie   MeSH
• virové proteiny chemie   genetika   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH