Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease.
The Gag-Pol polyprotein of human immunodeficiency virus type 1 is not required for efficient viral particle assembly or release. However, in this report we demonstrate that the synthesis of a truncated Gag-Pol precursor due to a premature termination codon in pol can reduce the ability of a full-length provirus to direct the formation of viral particles. Marked effects on particle production were seen when premature termination codons were introduced into the integrase (IN)-coding region. By contrast, a mutant which lacked both IN and reverse transcriptase (RT) formed particles with normal efficiency. Particle production by IN mutants was restored to wild-type levels when a second premature termination codon was introduced at the 5' end of the RT-coding sequence. Particle formation was similarly restored by a second site mutation in the viral protease (PR) gene which prevented proteolytic processing of the Gag polyprotein. Finally particle formation was restored in the presence of A77003, a specific inhibitor of human immunodeficiency virus type 1 PR. These results suggest that the effects of a lack of IN sequences on particle formation require the synthesis of a Gag-Pol precursor which contains RT sequences and are due to inappropriate PR activity.
Bukovsky
A
A
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Göttlinger
H
H
D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008782:Methylurea Compounds / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D011725:Pyridines / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives; D019065:Virus Assembly; D016662:Virus Integration
D017320:HIV Protease Inhibitors; D008782:Methylurea Compounds; D011725:Pyridines; C079555:Abbott 77003; D019426:Integrases; D010450:Endopeptidases; D014633:Valine