title: Ligand passing by the p75 tumour necrosis factor receptor enhances HIV-1 activation.
abstract: Recently, a HIV-dependent upmodulation of the p75 tumour necrosis factor receptor (TNFr75) was observed using latently-infected OM-10.1 promyelocytes; although the participation of TNFr75 in HIV-1 activation remained undefined. Here, using receptor cross-linking by agonistic antibodies, no direct HIV-1 activation via TNFr75 was observed. Signalling via the p55 tumour necrosis factor receptor (TNFr55) accounted for the full extent of HIV-1 activation in OM-10.1 cultures. However, in tumour necrosis factor alpha (TNF-alpha) dose titration experiments, antibody blockade of TNFr75 decreased the dose response markedly, indicating a ligand passing function. TNFr75 blockade did not alter the dose response to agonistic TNFr55 antibody induction; verifying that the effect on the TNF-alpha dose response was not due to negative signalling or cytolysis. These results demonstrate that, although not directly involved in signal transduction resulting in HIV-1 activation, TNFr75 can serve a critical ligand passing function and permit continued HIV-1 expression during limited TNF-alpha availability.
authors.affiliation: Retrovirus Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. stb3@ciddasl.em.cdc.gov
authors.forename: S T
authors.initials: ST
authors.lastname: Butera
authors.forename: B D
authors.initials: BD
authors.lastname: Roberts
authors.forename: T M
authors.initials: TM
authors.lastname: Folks
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D015497:HIV-1 / Q000254:growth & development*; D018922:HL-60 Cells; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D014775:Virus Activation
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha