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

The enzymatic activity of the human immunodeficiency type 1 (HIV-1) pr otease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) va riants of the HIV-1 PR might be an alternative to current pharmacologi cal and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-ce ll lines were generated which constitutively expressed HIV-1 td PR var iants. 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 iso late bearing a PR inhibitor-resistant PR was blocked, showing that gen etic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.