An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_0006291X_v393_n4_p625_Garcia |
| Aporte de: |
| id |
todo:paper_0006291X_v393_n4_p625_Garcia |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_0006291X_v393_n4_p625_Garcia2023-10-03T14:03:57Z An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein García, C.C. Topisirovic, I. Djavani, M. Borden, K.L.B. Damonte, E.B. Salvato, M.S. Antiviral disulfide agent Arenavirus Lymphocytic choriomeningitis virus Promyelocytic leukemia protein RING-finger interactions Z protein antivirus agent arenavirus z protein disulfide mutant protein nsc 20625 promyelocytic leukemia protein unclassified drug virus protein article binding site cell nucleus inclusion body cell strain HepG2 controlled study genetic transfection human human cell Lymphocytic choriomeningitis virus nonhuman priority journal protein domain protein protein interaction Antiviral Agents Arenaviridae Infections Carrier Proteins Cell Line Disulfides Guanidines Humans Lymphocytic choriomeningitis virus Nuclear Proteins Transcription Factors Tumor Suppressor Proteins Arenavirus Lymphocytic choriomeningitis virus The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0006291X_v393_n4_p625_Garcia |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antiviral disulfide agent Arenavirus Lymphocytic choriomeningitis virus Promyelocytic leukemia protein RING-finger interactions Z protein antivirus agent arenavirus z protein disulfide mutant protein nsc 20625 promyelocytic leukemia protein unclassified drug virus protein article binding site cell nucleus inclusion body cell strain HepG2 controlled study genetic transfection human human cell Lymphocytic choriomeningitis virus nonhuman priority journal protein domain protein protein interaction Antiviral Agents Arenaviridae Infections Carrier Proteins Cell Line Disulfides Guanidines Humans Lymphocytic choriomeningitis virus Nuclear Proteins Transcription Factors Tumor Suppressor Proteins Arenavirus Lymphocytic choriomeningitis virus |
| spellingShingle |
Antiviral disulfide agent Arenavirus Lymphocytic choriomeningitis virus Promyelocytic leukemia protein RING-finger interactions Z protein antivirus agent arenavirus z protein disulfide mutant protein nsc 20625 promyelocytic leukemia protein unclassified drug virus protein article binding site cell nucleus inclusion body cell strain HepG2 controlled study genetic transfection human human cell Lymphocytic choriomeningitis virus nonhuman priority journal protein domain protein protein interaction Antiviral Agents Arenaviridae Infections Carrier Proteins Cell Line Disulfides Guanidines Humans Lymphocytic choriomeningitis virus Nuclear Proteins Transcription Factors Tumor Suppressor Proteins Arenavirus Lymphocytic choriomeningitis virus García, C.C. Topisirovic, I. Djavani, M. Borden, K.L.B. Damonte, E.B. Salvato, M.S. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| topic_facet |
Antiviral disulfide agent Arenavirus Lymphocytic choriomeningitis virus Promyelocytic leukemia protein RING-finger interactions Z protein antivirus agent arenavirus z protein disulfide mutant protein nsc 20625 promyelocytic leukemia protein unclassified drug virus protein article binding site cell nucleus inclusion body cell strain HepG2 controlled study genetic transfection human human cell Lymphocytic choriomeningitis virus nonhuman priority journal protein domain protein protein interaction Antiviral Agents Arenaviridae Infections Carrier Proteins Cell Line Disulfides Guanidines Humans Lymphocytic choriomeningitis virus Nuclear Proteins Transcription Factors Tumor Suppressor Proteins Arenavirus Lymphocytic choriomeningitis virus |
| description |
The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved. |
| format |
JOUR |
| author |
García, C.C. Topisirovic, I. Djavani, M. Borden, K.L.B. Damonte, E.B. Salvato, M.S. |
| author_facet |
García, C.C. Topisirovic, I. Djavani, M. Borden, K.L.B. Damonte, E.B. Salvato, M.S. |
| author_sort |
García, C.C. |
| title |
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| title_short |
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| title_full |
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| title_fullStr |
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| title_full_unstemmed |
An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein |
| title_sort |
antiviral disulfide compound blocks interaction between arenavirus z protein and cellular promyelocytic leukemia protein |
| url |
http://hdl.handle.net/20.500.12110/paper_0006291X_v393_n4_p625_Garcia |
| work_keys_str_mv |
AT garciacc anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT topisirovici anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT djavanim anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT bordenklb anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT damonteeb anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT salvatoms anantiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT garciacc antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT topisirovici antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT djavanim antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT bordenklb antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT damonteeb antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein AT salvatoms antiviraldisulfidecompoundblocksinteractionbetweenarenaviruszproteinandcellularpromyelocyticleukemiaprotein |
| _version_ |
1807321270562324480 |