Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
MOLECULAR BIOLOGY OF HTLV-I: BIOLOGICAL SIGNIFICANCE OF VIRAL GENES IN ITS REPLICATION AND LEUKEMOGENESIS
Retrovirus Biology and Human Disease. Gallo RC and Wong-Staal F, eds. New York, Marcel Dekker, p. 161-86, 1990.. Unique Identifier : AIDSLINE ICDB/91676223 Yoshida M; Seiki M; Dept. of Viral Oncology, Cancer Inst., Kami-Ikebukuro,; Toshima-ku, Tokyo, Japan
Abstract:
Based on results obtained in studies of animal retroviruses, researchers have expected examination of human T-cell leukemia virus type 1 (HTLV-I) and acute T-cell leukemia (ATL) to yield information concerning tumorigenesis in humans. The authors' studies on the molecular biology of HTLV-I are reviewed, with emphasis on the functions of pX and env genes and their significance in ATL development and its prevention. Topics include etiology of ATL, transacting viral function for ATL development, genomic structure and gene products, the envelope gene product (characterization of the product, its functions, and uses of the env protein), pX gene products and the mechanism of their expression, functions of pX proteins, transactivation of interleukin-2 (IL-2) receptor gene, significance of IL-2 receptor gene activation by tax, and a multistep model of ATL progression. Molecular biology studies on HTLV-I have clarified the regulatory mechanism of the viral gene expression and replication and have indicated the possible mechanism involved in the early stage of ATL development. The envelope gene of HTLV-I has been expressed in bacteria as fusion proteins and produced in large quantity. These fusion proteins are useful as diagnostic reagents and vaccine to prevent HTLV-I infection. The extra sequence 'pX' is a self-regulatory sequence that exerts positive and negative controls on viral gene expression. Two genes, tax and rex, are involved in these regulations and their functions have been characterized. The tax gene codes for p40tax, which is a transactivator of transcription of the HTLV-I genome activating an enhancer in the long terminal repeat. The tax also activates the cellular IL-2 receptor alpha (Tac antigen) in certain T-cell lines responding to the 5' regulatory sequences. This activation of the IL-2R gene may account for early events in ATL development. The rex gene codes for p27rex, which is a post-transcriptional regulator required for expression of the gag, pol, and env proteins. The rex increases the levels of unspliced mRNAs. The rex mediates a feedback control of viral gene transcription. Thus, rex makes the viral gene expression transient and the infected cell can escape from host immune response. Two transacting regulatory systems of HTLV-I resemble those of HIV in regulating viral replication, but the functional mechanisms seem to differ. (71 Refs)
Keywords: *Cloning, Molecular Gene Expression Regulation, Leukemic/*PHYSIOLOGY Gene Expression Regulation, Viral/*PHYSIOLOGY Genes, pX/GENETICS Genes, Viral/*GENETICS Human HTLV-I/*GENETICS Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/*MICROBIOLOGY Proviruses/GENETICS Receptors, Interleukin-2/GENETICS Transcription, Genetic/GENETICS Virus Replication/*GENETICS MONOGRAPH REVIEW
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
