Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The dynamics of human T-lymphotropic virus type-1 (HTLV-1) provirus expression in vivo are unknown. There is much evidence to suggest that HTLV-1 gene expression is restricted: this restricted gene expression may contribute to HTLV-1 persistence by limiting the ability of the HTLV-1-specific CD8(+) cell immune response to clear infected cells. In this study, we tested the hypothesis that derepression of HTLV-1 gene expression would allow an increase in CD8(+) cell-mediated lysis of HTLV-1-infected cells. Using histone deacetylase enzyme inhibitors (HDIs) to hyperacetylate histones and increase HTLV-1 gene expression, we found that HDIs doubled Tax expression in naturally infected lymphocytes after overnight culture. However, the rate of CD8(+) cell-mediated lysis of Tax-expressing cells ex vivo was halved. HDIs appeared to inhibit the CD8(+) cell-mediated lytic process itself, indicating a role for the microtubule-associated HDAC6 enzyme. These observations indicate that HDIs may reduce the efficiency of cytotoxic T-cell (CTL) surveillance of HTLV-1 in vivo. The impact of HDIs on HTLV-1 proviral load in vivo cannot be accurately predicted because of the widespread effects of these drugs on cellular processes; we therefore recommend caution in the use of HDIs in nonmalignant cases of HTLV-1 infection.

Original publication

DOI

10.1182/blood-2006-03-013235

Type

Journal article

Journal

Blood

Publication Date

01/12/2006

Volume

108

Pages

3801 - 3807

Keywords

CD8-Positive T-Lymphocytes, Cells, Cultured, Cohort Studies, Enzyme Inhibitors, Female, Gene Expression Regulation, Viral, Gene Products, tax, HTLV-I Infections, Histone Deacetylase Inhibitors, Histone Deacetylases, Human T-lymphotropic virus 1, Humans, Immunity, Cellular, Male, Proviruses