Mycobacterium tuberculosis and its purified protein derivative activate expression of the human immunodeficiency virus.
To examine the effects of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) expression, the monocytoid cell line U1 containing integrated provirus was incubated with the H37Ra strain of M. tuberculosis. This resulted in heightened expression of virus in supernatant that was partially inhibited by antibody to tumor necrosis factor-alpha (TNF-alpha). Purified protein derivative (PPD) prepared from M. tuberculosis also could activate HIV expression, and this was less affected by anti-TNF antibody. PPD could activate the HIV promoter in both U937, the monocytoid cell line from which U1 was derived, and Jurkat, a CD4+ lymphoid line. Activation was abolished by mutations in the nuclear factor (NF)-kB binding domains. Jurkat cells transfected with a plasmid construct linking 8 NF-kB binding domains to the chloramphenicol acetyltransferase (CAT) gene showed increased activity of the reporter gene after activation with PPD. Transcriptional activation of HIV expression by mycobacteria and mycobacterial products may enhance propagation of HIV in monocytoid and lymphoid cells. This may result in accelerated HIV disease progression in persons coinfected with M. tuberculosis.
Lederman
M M
MM
Department of Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio 44106-4984.
Georges
D L
DL
Kusner
D J
DJ
Mudido
P
P
Giam
C Z
CZ
Toossi
Z
Z
D001483:Base Sequence; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D016385:TATA Box; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014373:Tuberculin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha