Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
TRANSACTIVATOR GENES OF HTLV-I, II, AND III
Oncogenes and Growth Control. Kahn P et al, eds. New York, Springer-Verlag, p. 247-52, 1986.. Unique Identifier : AIDSLINE ICDB/87637993 Haseltine WA; Sodroski J; Rosen C; Goh WC; Dayton A; Celander D; Dana Farber Cancer Inst., Dept. of Pathology, Harvard Medical; Sch., Boston, MA 02115
Abstract:
Trans-activating genes found in the human T lymphotropic viruses (HTLVs) I, II, and III are reviewed with respect to structure, mechanism of action, and their role in the virus life cycle. The product of the longest open reading frame of HTLV-I and II corresponds to the transactivator (tat) protein; the rate of expression of HTLV-I genes is accelerated 50- to 200-fold in cells that constitutively express the tat protein. Experiments in which tat II gene was introduced into T4+ cell lines and the expression of genes encoding interleukin 2 (IL2) and IL2 receptor was measured showed that mRNA for both genes is induced by the tat II protein in these cells but not in B cell lines; moreover, functional IL2 and IL2 receptors could be demonstrated in T4+ lines that produced tat II protein, whereas cell lines containing the same sequences but in an inactive configuration remained negative. These findings suggest that the tat gene initiates transformation of T4+ cell by the induction of IL2 and IL2 receptors. The authors speculate that the mechanisms that normally limit the expansion of an activated T cell population may also limit the expansion of HTLV-I- and HTLV-II-infected T cells. If the infected T4+ cell is the infectious unit, expansion of the infected population by stimulation of a T4+ specific autocrine proliferation pathway would provide an obvious selective advantage to the virus. In this view, lymphomas induced by HTLV-I and II would be consequences of the mode of virus propagation. HTLV-III viruses deleted for the tat III gene show a greater than 500-fold reduction in the expression of the gag and env gene products relative to viruses containing the gene. Once replication begins, the tat III gene product should greatly accelerate the rate of synthesis of virus protein by an autocatalytic process limited only by the amount of viral RNA. The tat III gene may also play a role in the maintenance of the latent state observed after infection of nondividing T4+ cells. It is possible that resting, HTLV-III-infected T4+ cells express a cellular factor that suppresses tat III activity with the consequence that viral RNA, but no virus progeny, is produced. Relief from such an antagonist (eg, by T cell activation) could induce rapid virus replication. The ability of the HTLV-III virus to proliferate rapidly as a result of the induction of transactivator function probably plays an important role in the transmission and progression of HTLV-III-induced disease. (30 Refs)
Keywords: Cell Line Cell Transformation, Neoplastic *Gene Expression Regulation Genes, Viral Human HTLV-BLV Viruses/*GENETICS Retroviridae Proteins/*GENETICS Virus Replication MONOGRAPH
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
