Picking Some News about the Retroviral Vector World from the 9th Symposium of the European Society of Gene Therapy

The 9th symposium of the European Society of Gene Therapy (ESGT) organized by Murat Tuncer (President of the Meeting), Bernd Gansbacher (President of the ESGT), and Meral Ozguc (Secretary of the Meeting) took place in Antalya, South Turkey, on 2–4 November 2001. Although the international political context made difficult the coming of some researchers, this symposium has drawn an interesting picture of the works in progress in Europe and in the Mediterranean area

Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep

BACKGROUND: During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts. RESULTS: In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303) replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303) had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset. CONCLUSION: Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression of viral gene expression is a contributory factor in the impairment of immune surveillance and the uncontrolled proliferation of the BLV-infected tumor cell.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity

Colitis involves immune cell–mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)γ antagonist. We further demonstrate that Vanin-1, by antagonizing PPARγ, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease

Le transfert de genes par infection retrovirale dans l'analyse de la differenciation hematopoietique aviaire. Developpement et utilisation du marqueur LacZ

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 81388 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Silencing and overexpression of human blood group antigens in transfusion: Paving the way for the next steps.

International audienceIn the field of transfusion, controlling expression of blood group system antigens on the surface of RBCs has been envisioned as a major research objective for five decades. With the advent of gene transfer techniques in the 1980s, genetic manipulation acquired the tools and know-how necessary to propose this goal along with other strategies. Besides the use of gene transfer to study blood group antigens and to develop tools for transfusion purposes, since the beginning of the new millennium, technological advances in combination with the recognition of the clinical potential of gene transfer have led the transfusion domain into development of cell therapy approaches for therapeutic purposes based on genetic manipulation

Can genetic engineering of red blood cells and transfusion become close friends?

International audienc