FUNCTIONAL COMPARISON OF THE BASIC DOMAINS OF THE TAT PROTEINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 IN TRANS ACTIVATION

被引:28
作者
ELANGOVAN, B [1 ]
SUBRAMANIAN, T [1 ]
CHINNADURAI, G [1 ]
机构
[1] ST LOUIS UNIV,SCH MED,INST MOLEC VIROL,3681 PK AVE,ST LOUIS,MO 63110
关键词
D O I
10.1128/JVI.66.4.2031-2036.1992
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The trans-activator Tat proteins coded by human immunodeficiency virus type 1 (HIV-1) and HIV-2 appear to be similar in structure and function. However, the Tat protein of HIV-2 (Tat2) activates the HIV-1 long terminal repeat (LTR) less efficiently than Tat1 (M. Emerman, M. Guyader, L. Montagnier, D. Baltimore, and M. A. Muesing, EMBO J. 6:3755-3760, 1987). To determine the functional domain of Tat2 which contributes to this incomplete reciprocity, we have carried out domain substitution between Tat1 and Tat2 by exchanging the basic domains involved in Tat interaction with its target trans-activation-response (TAR) RNA structure. Our results indicate that Tat1 proteins containing substitutions of either 8 or 14 amino acids of the basic domain of Tat2 exhibited reduced trans activation of the HIV-1 LTR by about 1/20 or one-fourth the level induced by wt Tat1. In contrast, Tat2 containing a substitution of the 9-amino-acid basic domain of Tat1 trans activated HIV-1 LTR like native Tat1. A substitution of the highly conserved core domain of Tat2 with that of Tat1 did not have any significant effect on trans activation of the HIV-1 LTR. These results indicate that the basic domain of Tat2 contributes to its inefficient trans activation of the HIV-1 LTR. Mutation of an acidic residue (Glu) located between the core domain and the Arg-rich basic domain of Tat2 at position 77 to a Gly residue increased the activity of Tat2 substantially. These results further suggest that the presence of an acidic residue (Glu) adjacent to Arg-rich sequences may at least partially contribute to the reduced activity of the Tat2 basic domain.
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页码:2031 / 2036
页数:6
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