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) 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.
Progenesys Program at Systemix, Palo Alto, California 94304, USA.
U
U
Junker
S
S
Escaich
I
I
Plavec
J
J
Baker
F
F
McPhee
J R
JR
Rose
C S
CS
Craik
E
E
Böhnlein
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002460:Cell Line; D004352:Drug Resistance, Microbial; D015870:Gene Expression; D014644:Genetic Variation; D016333:HIV Protease / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008782:Methylurea Compounds / Q000494:pharmacology; D010957:Plasmids; D011480:Protease Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives; D014779:Virus Replication
D008782:Methylurea Compounds; D011480:Protease Inhibitors; D011725:Pyridines; C079555:Abbott 77003; D016333:HIV Protease; D014633:Valine