title: Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles.
abstract: 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.
authors.affiliation: Animal Models & Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andresen
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Pise-Masison
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha-Datta
authors.forename: Marcia
authors.initials: M
authors.lastname: Bellon
authors.forename: Valerio
authors.initials: V
authors.lastname: Valeri
authors.forename: Robyn
authors.initials: R
authors.lastname: Washington Parks
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecchinato
authors.forename: Risaku
authors.initials: R
authors.lastname: Fukumoto
authors.forename: Christophe
authors.initials: C
authors.lastname: Nicot
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D051336:Mitochondrial Membranes / Q000378:metabolism; D011485:Protein Binding; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D016356:Gene Products, tax; D012191:Retroviridae Proteins; C072813:rof protein, Human T-lymphotropic virus 1; C514970:tax protein, Human T-lymphotrophic virus 1; D050880:p300-CBP Transcription Factors