Inhibition of HIV-1 or bacterial activation of macrophages by products of HIV-1-resistant human cells.
We have recently described the molecular basis of HIV-1 resistance factor (HRF)-mediated anti-viral activity in primary and transformed CD4 T cells. HRF+ cell culture supernatants or partially purified HRF were found to incapacitate the formation of the NF-kappaB/DNA complex, which is indispensable for long terminal promoter-driven transcription of virus genes. In this study, we tested whether HRF might have much broader activity against other organisms whose pathogenesis is linked to NF-kappaB activation. Specifically, we tested the effects of HRF on the NF-kappaB-mediated responses of primary macrophages to HIV-1 or several bacterial antigens. We found that exposure to HRF inhibited HIV-1 expression in macrophages and also induced the production of HRF-like activity by macrophages, which prevented replication of virus in HIV-1-infected peripheral blood lymphocytes cultured in the adjacent compartment. We investigated the mechanism of this inhibition and found that HRF impeded NF-kappaB/DNA binding in macrophages induced by either HIV-1 or lipopolysaccharide from several bacteria species, resulting in impaired tumor necrosis factor-alpha responses to these organisms.
Li
Guanhua
G
Molecular Virology Division, St Luke's-Roosevelt Hospital Center, Columbia University Medical Center, New York, NY, USA.
Aaron
Sagiv
S
Kazmierczak
Katarzyna
K
Lesner
Adam
A
Li
Yuchang
Y
Ivanova
Anna
A
Bentsman
Galina
G
Potash
Mary Jane
MJ
Simm
Malgorzata
M
D001419:Bacteria / Q000187:drug effects / Q000276:immunology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D004247:DNA