title: Inhibition of HIV-1 or bacterial activation of macrophages by products of HIV-1-resistant human cells.
abstract: 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.
authors.affiliation: Molecular Virology Division, St Luke's-Roosevelt Hospital Center, Columbia University Medical Center, New York, NY, USA.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Li
authors.forename: Sagiv
authors.initials: S
authors.lastname: Aaron
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kazmierczak
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Li
authors.forename: Anna
authors.initials: A
authors.lastname: Ivanova
authors.forename: Galina
authors.initials: G
authors.lastname: Bentsman
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Potash
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Simm
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D004247:DNA