Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines

J Virol. 1996 Nov;70(11):7765-72. doi: 10.1128/JVI.70.11.7765-7772.1996.


The enzymatic activity of the human immunodeficiency type 1 (HIV-1) protease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) variants of the HIV-1 PR might be an alternative to current pharmacological and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-cell lines were generated which constitutively expressed HIV-1 td PR variants. HIV-1 infection experiments demonstrated severely reduced HIV-1 replication in these td PR CEM-SS cell lines compared with control T cells expressing wild-type PR. Furthermore, replication of an HIV-1 isolate bearing a PR inhibitor-resistant PR was blocked, showing that genetic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • Cell Line
  • Drug Resistance, Microbial
  • Gene Expression
  • Genetic Variation*
  • HIV Protease / drug effects
  • HIV Protease / genetics
  • HIV Protease / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Methylurea Compounds / pharmacology
  • Plasmids
  • Protease Inhibitors / pharmacology
  • Pyridines / pharmacology
  • Valine / analogs & derivatives
  • Virus Replication*


  • Methylurea Compounds
  • Protease Inhibitors
  • Pyridines
  • Abbott 77003
  • HIV Protease
  • Valine