Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon
The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apo...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2010 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/6965 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/6965 |
| Access Level: | acceso abierto |
| Palabra clave: | Cell Proliferation Chemotaxis Computational Biology Cytoskeleton Exons Gene Expression HIV-1 Humans Jurkat Cells Models, Molecular Receptors, Cell Surface Transcriptional Activation tat Gene Products, Human Immunodeficiency Virus |
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Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exonLopez-Huertas, Maria RosaCallejas, S.Abia, DavidMateos, ElenaDopazo, A.Alcamí, JoséCoiras, MayteCell ProliferationChemotaxisComputational BiologyCytoskeletonExonsGene ExpressionHIV-1HumansJurkat CellsModels, MolecularReceptors, Cell SurfaceTranscriptional Activationtat Gene Products, Human Immunodeficiency VirusThe human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1-72aa) is sufficient for viral transcript elongation and second exon (73-101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-kappaB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat-Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells.Oxford University PressPlan Nacional sobre el Sida (España)Fundación para la Investigación y la Prevención del Sida en EspañaComunidad de Madrid (España)Instituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)20182018-12-2720102010-02-0520102010-02-05research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6965reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES MVI1434 05–5ES PI040614 Not availableES PI0808752 Not availableES BIO2008-04384 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/69652026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| title |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| spellingShingle |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon Lopez-Huertas, Maria Rosa Cell Proliferation Chemotaxis Computational Biology Cytoskeleton Exons Gene Expression HIV-1 Humans Jurkat Cells Models, Molecular Receptors, Cell Surface Transcriptional Activation tat Gene Products, Human Immunodeficiency Virus |
| title_short |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| title_full |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| title_fullStr |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| title_full_unstemmed |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| title_sort |
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon |
| dc.creator.none.fl_str_mv |
Lopez-Huertas, Maria Rosa Callejas, S. Abia, David Mateos, Elena Dopazo, A. Alcamí, José Coiras, Mayte |
| author |
Lopez-Huertas, Maria Rosa |
| author_facet |
Lopez-Huertas, Maria Rosa Callejas, S. Abia, David Mateos, Elena Dopazo, A. Alcamí, José Coiras, Mayte |
| author_role |
author |
| author2 |
Callejas, S. Abia, David Mateos, Elena Dopazo, A. Alcamí, José Coiras, Mayte |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Plan Nacional sobre el Sida (España) Fundación para la Investigación y la Prevención del Sida en España Comunidad de Madrid (España) Instituto de Salud Carlos III Ministerio de Ciencia e Innovación (España) |
| dc.subject.none.fl_str_mv |
Cell Proliferation Chemotaxis Computational Biology Cytoskeleton Exons Gene Expression HIV-1 Humans Jurkat Cells Models, Molecular Receptors, Cell Surface Transcriptional Activation tat Gene Products, Human Immunodeficiency Virus |
| topic |
Cell Proliferation Chemotaxis Computational Biology Cytoskeleton Exons Gene Expression HIV-1 Humans Jurkat Cells Models, Molecular Receptors, Cell Surface Transcriptional Activation tat Gene Products, Human Immunodeficiency Virus |
| description |
The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1-72aa) is sufficient for viral transcript elongation and second exon (73-101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-kappaB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat-Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells. |
| publishDate |
2010 |
| dc.date.none.fl_str_mv |
2010 2010-02-05 2010 2010-02-05 2018 2018-12-27 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/6965 |
| url |
http://hdl.handle.net/20.500.12105/6965 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
ES MVI1434 05–5 ES PI040614 Not available ES PI0808752 Not available ES BIO2008-04384 Not available |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución-NoComercial-CompartirIgual 4.0 Internacional http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución-NoComercial-CompartirIgual 4.0 Internacional http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Oxford University Press |
| publisher.none.fl_str_mv |
Oxford University Press |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
| instname_str |
Instituto de Salud Carlos III (ISCIII) |
| reponame_str |
Repisalud |
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Repisalud |
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1869412718906179585 |
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15,812429 |