Reference : Opposite effects of valproate on Tax and HBZ expressions in T-lymphocytes from HTLV-1...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/104324
Opposite effects of valproate on Tax and HBZ expressions in T-lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients.
English
Belrose, Gildas [ > > ]
Gross, Antoine [ > > ]
Olindo, Stéphane [ > > ]
Lézin, Agnès [ > > ]
Dueymes, Maryvonne [ > > ]
Komla-Soukha, Isabelle [ > > ]
Smadja, Didier [ > > ]
Tanaka, Yuetsu [ > > ]
Willems, Luc mailto [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc. >]
Mesnard, Jean-Michel [ > > ]
Peloponese, Jean-Marie [ > > ]
Césaire, Raymond [ > > ]
1-Sep-2011
Blood
American Society of Hematology
118
9
2483-2491
Yes (verified by ORBi)
International
0006-4971
1528-0020
Washington
DC
[en] A determinant of human T-lymphotropic virus-1 (HTLV-1)–associated myelopathy/ tropical spastic paraparesis (HAM/TSP) development is the HTLV-1–infected cell burden. Viral proteins Tax and HBZ, encoded by the sense and antisense strands of th pX region, respectively, play key roles in HTLV-1 persistence. Tax drives CD4 - cel clonal expansion and is the immunodominant viral antigen recognized by the immune response. Valproate (2-n-propylpentanoic acid, VPA), a histone deacetylase inhibitor, was thought to trigger Tax expression, thereby exposing the latent HTLV-1 reservoir to immune destruction. We evaluated the impact of VPA on Tax, Gag, and HBZ expressions in cultured lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients. Approximately one-fifth of proviruspositive CD4 T cells spontaneously became Tax-positive, but this fraction rose to two-thirds of Tax positive–infected cells when cultured with VPA. Valproate enhanced Gag-p19 release. Tax- and GagmRNA levels peaked spontaneously, before declining concomitantly to HBZmRNA increase. VPA enhanced and prolonged Tax-mRNA expression, whereas it blocked HBZ expression. Our findings suggest that, in addition to modulating Tax expression, another mechanism involving HBZ repression might determine the outcome ofVPAtreatment on HTLV-1–infected– cell proliferation and survival.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/104324
10.1182/blood-2010-11-321364

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