title: Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.
abstract: The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.
authors.affiliation: Department of Clinical and Biological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pilotti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Mortara
authors.forename: Andrea
authors.initials: A
authors.lastname: De Lerma Barbaro
authors.forename: Claudio
authors.initials: C
authors.lastname: Casoli
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Accolla
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D014779:Virus Replication; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C083728:MHC class II transactivator protein; C402244:nuclear factor Y