Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection.
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(+)...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2006
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| _version_ | 1797075141335711744 |
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| author | Mosley, A Meekings, K McCarthy, C Shepherd, D Cerundolo, V Mazitschek, R Tanaka, Y Taylor, G Bangham, C |
| author_facet | Mosley, A Meekings, K McCarthy, C Shepherd, D Cerundolo, V Mazitschek, R Tanaka, Y Taylor, G Bangham, C |
| author_sort | Mosley, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:46:08Z |
| format | Journal article |
| id | oxford-uuid:70f534c3-f1f3-46e2-9fa1-048aec60d00b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:46:08Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:70f534c3-f1f3-46e2-9fa1-048aec60d00b2022-03-26T19:40:40ZHistone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70f534c3-f1f3-46e2-9fa1-048aec60d00bEnglishSymplectic Elements at Oxford2006Mosley, AMeekings, KMcCarthy, CShepherd, DCerundolo, VMazitschek, RTanaka, YTaylor, GBangham, CThe 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. |
| spellingShingle | Mosley, A Meekings, K McCarthy, C Shepherd, D Cerundolo, V Mazitschek, R Tanaka, Y Taylor, G Bangham, C Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title | Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title_full | Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title_fullStr | Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title_full_unstemmed | Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title_short | Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. |
| title_sort | histone deacetylase inhibitors increase virus gene expression but decrease cd8 cell antiviral function in htlv 1 infection |
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