Immune Netw.  2002 Sep;2(3):150-157. 10.4110/in.2002.2.3.150.

A Human Immunodeficiency Virus Type 1 (HIV-1) Tat Cofactor Absent in Rodent Cells is a TAR-associated Factor

• Lee IS
• Shank PR

• KMID: 1571517
• DOI: http://doi.org/10.4110/in.2002.2.3.150

Abstract

BACKGROUND: Although Tat plays a role as a potent transactivator in the viral gene expression from the Human Immunodeficiency Virus type 1 long terminal repeat (HIV-1 LTR), it does not function efficiently in rodent cells implying the absence of a human specific factor essential for Tat-medicated transactivation in rodent cells. In previous experiments, we demonstrated that one of chimeric forms of TAR (transacting responsive element) of HIV-1 LTR compensated the restriction in rodent cells.
METHODS
To characterize the nature of the compensation, we tested the effects of several upstream binding factors of HIV-1 LTR by simple substitution, and also examined the role of the configuration of the upstream binding factor(s) indirectly by constructing spacing mutants that contained insertions between Sp1 and TATA box on Tat-mediated transactivation.
RESULTS
Human Sp1 had no effect whereas its associated factors displayed differential effects in human and rodent cells. In addition, none of the spacing mutants tested overcame the restriction in rodent cells. Rather, when the secondary structure of the chimeric HIV-1 TAR construct was destroyed, the compensation in rodent cells was disappeared. Interestingly, the proper interaction between Sp1 and TATA box binding proteins, which is essential for Tat-dependent transcription, was dispensable in rodent cells.
CONCLUSION
This result suggests that the human-specific Tat cofactor acts to allow Tat to interact effectively in a ribonucleoprotein complex that includes Tat, cellular factors, and TAR RNA, rather than be associated with the HIV-1 LTR upstream DNA binding factors.

Keyword

Tat; transactivation; HIV-1-LTR; TAR

MeSH Terms

Compensation and Redress
DNA
Genes, Viral
HIV Long Terminal Repeat
HIV*
HIV-1*
Humans*
Ribonucleoproteins
RNA
Rodentia*
TATA Box
TATA-Box Binding Protein
Terminal Repeat Sequences
Trans-Activators
Transcriptional Activation
DNA
RNA
Ribonucleoproteins
TATA-Box Binding Protein
Trans-Activators