[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.
Disciplines :
Oncology
Author, co-author :
Belrose, Gildas
Gross, Antoine
Olindo, Stéphane
Lézin, Agnès
Dueymes, Maryvonne
Komla-Soukha, Isabelle
Smadja, Didier
Tanaka, Yuetsu
Willems, Luc ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Mesnard, Jean-Michel
Peloponese, Jean-Marie
Césaire, Raymond
Language :
English
Title :
Opposite effects of valproate on Tax and HBZ expressions in T-lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients.
Publication date :
01 September 2011
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
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