The Ribonucleotide Reductase R1 Subunits of Herpes Simplex Virus 1 and 2 Protect Cells against Poly(I · C)-Induced Apoptosis
| العنوان: | The Ribonucleotide Reductase R1 Subunits of Herpes Simplex Virus 1 and 2 Protect Cells against Poly(I · C)-Induced Apoptosis |
|---|---|
| المؤلفون: | Florent Dufour, Angela Pearson, Yves Langelier, Luc Bertrand, Nathalie Grandvaux |
| المساهمون: | Institut du Cancer de Montréal (ICM), Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Département de Biochimie, Département de Médecine, Faculté de Médecine, This work was supported by Canadian Institutes of Health Research grant NRF 67052. |
| المصدر: | Journal of Virology Journal of Virology, American Society for Microbiology, 2011, 85 (17), pp.8689-701. ⟨10.1128/JVI.00362-11⟩ |
| بيانات النشر: | American Society for Microbiology, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Herpesvirus 2, Human, viruses, Immunology, Apoptosis, Herpesvirus 1, Human, Cycloheximide, Biology, Caspase 8, MESH: Caspase 8, MESH: Poly I-C, Microbiology, HeLa, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interferon, Virology, Ribonucleotide Reductases, medicine, Humans, MESH: Protein Binding, MESH: Ribonucleotide Reductases, MESH: Humans, MESH: Apoptosis, RNA-Binding Proteins, Transfection, MESH: Protein Subunits, biology.organism_classification, Caspase Inhibitors, MESH: Herpesvirus 2, Human, Molecular biology, Virus-Cell Interactions, Cell biology, Nuclear Pore Complex Proteins, Protein Subunits, MESH: Herpesvirus 1, Human, Poly I-C, MESH: RNA-Binding Proteins, chemistry, TRIF, Insect Science, MESH: HeLa Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Tumor necrosis factor alpha, HeLa Cells, Protein Binding, MESH: Nuclear Pore Complex Proteins, medicine.drug |
| الوصف: | We recently provided evidence that the ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 (HSV-1 and -2) protect cells against tumor necrosis factor alpha- and Fas ligand-induced apoptosis by interacting with caspase 8. Double-stranded RNA (dsRNA) is a viral intermediate known to initiate innate antiviral responses. Poly(I · C), a synthetic analogue of viral dsRNA, rapidly triggers caspase 8 activation and apoptosis in HeLa cells. Here, we report that HeLa cells after HSV-1 and HSV-2 infection were quickly protected from apoptosis caused by either extracellular poly(I · C) combined with cycloheximide or transfected poly(I · C). Cells infected with the HSV-1 R1 deletion mutant ICP6Δ were killed by poly(I · C), indicating that HSV-1 R1 plays a key role in antiapoptotic responses to poly(I · C). Individually expressed HSV R1s counteracted caspase 8 activation by poly(I · C). In addition to their binding to caspase 8, HSV R1s also interacted constitutively with receptor-interacting protein 1 (RIP1) when expressed either individually or with other viral proteins during HSV infection. R1(1-834)-green fluorescent protein (GFP), an HSV-2 R1 deletion mutant protein devoid of antiapoptotic activity, did not interact with caspase 8 and RIP1, suggesting that these interactions are required for protection against poly(I · C). HSV-2 R1 inhibited the interaction between the Toll/interleukin-1 receptor domain-containing adaptor-inducing beta interferon (IFN-β) (TRIF) and RIP1, an interaction that is essential for apoptosis triggered by extracellular poly(I · C) plus cycloheximide or TRIF overexpression. TRIF silencing reduced poly(I · C)-triggered caspase 8 activation in mock- and ICP6Δ-infected cells, confirming that TRIF is involved in poly(I · C)-induced apoptosis. Thus, by interacting with caspase 8 and RIP1, HSV R1s impair the apoptotic host defense mechanism prompted by dsRNA. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::faf3002434d6a57e3fc9081293940de6Test https://doi.org/10.1128/jvi.00362-11Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....faf3002434d6a57e3fc9081293940de6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
|---|