Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication
| العنوان: | Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication |
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| المؤلفون: | Gabriele Hahn, Richard F. Greaves, Mercedes Reboredo |
| المصدر: | Journal of General Virology. 85:3555-3567 |
| بيانات النشر: | Microbiology Society, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | DNA Replication, Human cytomegalovirus, Chromosomes, Artificial, Bacterial, Programmed cell death, viruses, DNA replication, Cytomegalovirus, Apoptosis, Exons, Fibroblasts, Biology, Virus Replication, medicine.disease, Virology, Virus, Cell Line, Immediate-Early Proteins, Viral Proteins, Viral replication, Cell culture, medicine, Humans, Viral shedding |
| الوصف: | Human cytomegalovirus (HCMV) strain AD169 mutants carrying transposon insertions or large deletions in UL37 exon 1 (UL37x1) were recovered from modified bacterial artificial chromosomes by reconstitution in human fibroblasts expressing the adenovirus anti-apoptotic protein E1B19K. UL37x1 mutant growth was severely compromised in normal fibroblasts, with minimal release of infectious progeny. Growth in E1B19K-expressing cells was restored, but did not reach wild-type levels. Normal fibroblasts infected by UL37x1 mutants underwent apoptosis spontaneously between 48 and 96 h after infection. Apoptosis was inhibited by treatment of cells with the broad-spectrum caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone, resulting in substantially increased release of virus. Inhibition of viral DNA replication by phosphonoformate or ganciclovir also inhibited apoptosis, implying that death was triggered by late viral functions or by replication and packaging of the viral genome. Immunofluorescent staining showed that although viral proteins accumulated normally during delayed-early phase and viral DNA replication compartments formed, viral late proteins were detected only rarely, suggesting that spontaneous apoptosis occurs early in late phase. These results demonstrate that anti-apoptotic proteins encoded by HCMV UL37x1 [pUL37x1 (vMIA), gpUL37 and gpUL37(M)] prevent apoptosis that would otherwise be initiated by the replication programme of the virus and are required for efficient and sustainable virus replication. |
| تدمد: | 1465-2099 0022-1317 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dbdb99eb1ec703abb5af786fbd85b60e https://doi.org/10.1099/vir.0.80379-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dbdb99eb1ec703abb5af786fbd85b60e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14652099 00221317 |
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