Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE ROLE OF HTLV-1 GENES IN IMMORTALIZATION OF PRIMARY HUMAN CD4+ T LYMPHOCYTES (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Disease. October 6-11, 1991, Padova/Venice, Italy, p. 35, 1991.. Unique Identifier : AIDSLINE ICDB/92682391 Haseltine WA; Ramstedt U; Grassman R; Poznansky M; Sodroski J; McGuire K; Fleckenstein B; Dana Farber Cancer Inst., Harvard Medical Sch., Boston, MA
Abstract:
The human T-cell leukemia virus type 1 (HTLV-1) is capable of immortalizing primary human T cells in culture. The IL-2-dependent cell lines which result from infection with HIV-1 are large activated T lymphocytes that are CD3+, CD4+, CD5+, express high-affinity IL-2 receptors, and express a high concentration of surface class II antigen. It was originally proposed that the proteins encoded by the X region of the HTLV-1 genome activate cellular genes that alter the growth properties of the infected T cells. The region X contains multiple open reading frames, and 2 are known to specify functional proteins: the 42-kD transactivator (tax), and the 27-kD regulator of virion protein expression (rex). The hypothesis that these two proteins are responsible for immortalization of primary lymphocytes has been difficult to test using HTLV-1 itself, as both of these proteins are required for virus replication. We addressed this problem by inserting the X region into two different vectors: Herpesvirus saimiri devoid of its own transforming genes and the human immunodeficiency virus devoid of all HIV-1 structural and regulatory genes. The HIV-1-HTLV-1 recombinant genome is in progress. Previous studies with the H saimiri vector showed that infection of primary thymocytes and primary cord blood cells with the H saimiri-HTLV-1 X vector leads to clonal proliferation of immortal T cells that have an appearance and phenotype indistinguishable from that of cells transformed by HTLV-1 itself. This result is all the more remarkable as H saimiri can infect a broad range of human hematopoietic cells. In more recent studies mutants of the X region, which express only a subset of HTLV-1 X-region-encoded proteins, were inserted into H saimiri and used to infect primary lymphocyte cultures. Preliminary results of this experiment are reported. These studies will help us to define the role of tax and rex in immortalization of primary T cells. The preliminary results obtained using the HIV-1 vector system to deliver HTLV-1 X region genes to CD4+ primary T cells are also discussed. Additionally, a possible role of rex in activation of cellular genes involved in regulation of T-cell growth is illustrated.
Keywords: Cell Division *CD4-Positive T-Lymphocytes/PATHOLOGY Gene Products, rex/*GENETICS Gene Products, tax/*GENETICS Herpesvirus 2, Saimirine/*GENETICS Human HTLV-I/*GENETICS HTLV-I Infections/*GENETICS Viral Regulatory Proteins/GENETICS ABSTRACT 920930
M9290918
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
