Document 0714
 DOCN  M9650714
 TI    Function of exon 2 in optimal trans-activation by Tat of HIV type 2.
 DT    9605
 AU    Pagtakhan AS; Tong-Starksen SE; Department of Medicine, Veterans
       Administration Medical Center,; San Francisco, California, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Nov;11(11):1367-72. Unique Identifier :
       AIDSLINE MED/96159134
 AB    HIV-1 and HIV-2 are human retroviruses whose life cycles require viral
       regulatory proteins, one of which is the trans-activator, Tat. Tat of
       HIV-1 (Tat-1) displays modular function with independent activation
       function localized to the amino-terminal, cysteine-rich, and core
       regions and independent RNA-binding function localized to a basic
       region. These functional domains are contained in the first of two exons
       encoding Tat-1; deletion of exon 2 does not contribute to functional
       domains of Tat-1. Tat of HIV-2 (Tat-2) has structurally analogous
       regions, but the amino terminus, basic region, and carboxy terminus
       encoded by exon 2 display amino acid sequence and functional divergence
       compared to Tat-1. We have shown that, in contrast to Tat-1, exon 2 of
       Tat-2 (residues 100 to 130) is required for optimal trans-activation of
       HIV-1 and HIV-2 long terminal repeats (LTRs). Here we demonstrate that a
       series of basic residues in exon 2 are required for these effects. Exon
       2 does not alter the level of protein expression of Tat-2. Further, in
       the context of heterologous DNA binding, exon 2 does not contribute to
       activation function. These data suggest that full-length Tat-2 results
       in optimal trans-activation through enhanced RNA-binding function of
       exon 1 by involvement of a basic region in exon 2. Differential
       expression of short and full-length Tats during different stages of the
       HIV-2 life cycle might regulate levels of viral expression, viral
       replication, and resultant cytopathology.
 DE    Amino Acid Sequence  DNA, Viral  *Exons  Gene Products, tat/*GENETICS
       Human  HIV Long Terminal Repeat/GENETICS  HIV-1/GENETICS
       HIV-2/*GENETICS  Molecular Sequence Data  Support, Non-U.S. Gov't
       Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       *Trans-Activation (Genetics)  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).