Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
MOLECULAR STUDIES ON HTLV-1 GENE EXPRESSION ASSOCIATED WITH ADULT T-CELL LEUKEMIA AND TSP/HAM (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 106, 1991.. Unique Identifier : AIDSLINE ICDB/92682443 Yoshida M; Fujisawa J; Dept. of Cellular and Molecular Biology, Inst. of Medical Sci.,; Univ. of Tokyo, Shirokanedai, Minato-ku, Tokyo 108, Japan
Abstract:
Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL), and is also associated with tropical spastic paraparesia. Viral replication and gene expression are regulated by at least two viral transacting regulators, tax and rex, whose functions are also involved in development of ATL. Tax protein is a transcriptional activator that activates the viral enhancer consisting of 21 bp contained in the LTR. Tax also activates cellular genes such as those that code for IL-2, IL-2 receptor, GM-CSF, FOS, PTHrP and MHC class I. However, the promoter regions of these genes have no sequence homologies and TAX protein itself does not bind to these DNAs. Thus, cellular DNA-binding proteins have been proposed to be involved in these activations. A cellular DNA binding NF-kB was proposed for the activation of IL-2 receptor alpha gene. We have isolated and characterized cellular proteins (TREB) that bind to the 21-bp viral enhancer. TREB proteins contain leucine zipper and basic amino acid domain structure as is conserved in FOS, JUN and CREB family. The functions of the TREB proteins and their possible involvement in the tax activation are currently investigated. The other transregulator rex modulates RNA processing and stimulates the expression of unspliced mRNA that codes gag, pol and env. On the other hand, rex represses the expression of fully spliced tax/rex mRNA that codes two regulatory proteins, TAX and REX, thus accomplishing the viral gene expression transient. For these regulations, rex requires a specific sequence in the 3' LTR that forms a very stable secondary structure. Combination of transcriptional activation with tax and its repression by rex, modulating RNA processing, makes the viral gene expression transient and keeps it at a lower level, thus allowing HTLV-I-infected cells to escape from the host immune response. Thus, a regulatory system (tax and rex) contributes to accumulation of infected and abnormally growing T cells that should be an early stage of ATL development.
Keywords: *Gene Expression Gene Products, rex/GENETICS Gene Products, tax/GENETICS Human HIV Long Terminal Repeat HTLV-I/*GENETICS Leukemia, T-Cell/*GENETICS Paraparesis, Tropical Spastic/*GENETICS Receptors, Interleukin-2/GENETICS RNA, Messenger/GENETICS ABSTRACT 920830
M9281096
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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.
