Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles
| Autor: | Marcia Bellon, Valentina Cecchinato, Genoveffa Franchini, Risaku Fukumoto, Uma Sinha-Datta, Cynthia A. Pise-Masison, Robyn Washington Parks, Vibeke Andresen, Christophe Nicot, Valerio W. Valeri |
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| Rok vydání: | 2011 |
| Předmět: |
Gene Expression Regulation
Viral Viral protein Immunoprecipitation viruses Blotting Western Immunology Retroviridae Proteins Repressor Context (language use) Plasma protein binding Biology Virus Replication medicine.disease_cause Biochemistry Cell Line medicine Humans p300-CBP Transcription Factors Immunobiology Cell Nucleus Regulation of gene expression Human T-lymphotropic virus 1 Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction Gene Products tax Cell Biology Hematology biology.organism_classification Virology HEK293 Cells Viral replication Mitochondrial Membranes HeLa Cells Protein Binding |
| Zdroj: | Blood. 118:1549-1559 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Disease development in human T-cell leukemia virus type 1 (HTLV-1)–infected individuals is positively correlated with the level of integrated viral DNA in T cells. HTLV-1 replication is positively regulated by Tax and Rex and negatively regulated by the p30 and HBZ proteins. In the present study, we demonstrate that HTLV-1 encodes another negative regulator of virus expression, the p13 protein. Expressed separately, p13 localizes to the mitochondria, whereas in the presence of Tax, part of it is ubiquitinated, stabilized, and rerouted to the nuclear speckles. The p13 protein directly binds Tax, decreases Tax binding to the CBP/p300 transcriptional coactivator, and, by reducing Tax transcriptional activity, suppresses viral expression. Because Tax stabilizes its own repressor, these findings suggest that HTLV-1 has evolved a complex mechanism to control its own replication. Further, these results highlight the importance of studying the function of the HTLV-1 viral proteins, not only in isolation, but also in the context of full viral replication. |
| Databáze: | OpenAIRE |
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