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Inhibition of HIV-1 Replication by Mutant Tat Peptides

  • Paul M. Loewenstein
  • Masaho Ishino
  • Na’eem Abdullah
  • Maurice Green
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Summary

The HIV-1 Tat protein is a potent transactivator that is essential for virus replication. We reported previously that chemically synthesized Tat minimal domain peptides and full length Tat (Tat86), in which alanine is substituted for Lys-41, are taken up by cells and antagonize the expression of microinjected HIV-LTR driven CAT gene. We find that several Tat mutant peptides inhibit HIV-1 (HTLV-IIIB) replication. Tat86,41Ala, the most active peptide, inhibits virus replication 95–99% in acutely infected cells when added to the culture medium at concentrations of 10−6 M to 10−7 M; chronically infected cells are also inhibited but to a lesser extent. Tat86,41Ala protects HIV-1 infected cells from virus-induced cytopathogenicity and inhibits syncytia formation. The mechanism of inhibition by Tat mutant peptides is unknown. Unexpectedly, co-transfection of a Tat86 expressing plasmid with plasmids expressing Tat86,41Ala does not inhibit transactivation of endogenous HIV-LTRCAT in HeLa cells. Thus the Tat86,41Ala peptide, when added to cells together with Tat86 can block HIV-LTRCAT transactivation, but not when expressed endogenously from a plasmid. These results imply a novel mechanism of Tat antagonism.

Keywords

Human Immunodeficiency Virus Transactivation Activity Molt4 Cell Syncytium Formation Fusion Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Paul M. Loewenstein
    • 1
  • Masaho Ishino
    • 1
  • Na’eem Abdullah
    • 1
  • Maurice Green
    • 1
  1. 1.Institute for Molecular VirologySt. Louis University School of MedicineSt. LouisUSA

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