title: Attachment of human immunodeficiency virus-1 (HIV-1) particles bearing host-encoded B7-2 proteins leads to nuclear factor-kappa B- and nuclear factor of activated T cells-dependent activation of HIV-1 long terminal repeat transcription.
abstract: Previous studies have shown that human immunodeficiency virus type-1 (HIV-1) can incorporate several surface proteins of host origin. Recent findings indicate that host-encoded cell surface constituents retain their functionality when found embedded into the viral envelope. The primary objective of the current study was to define whether interaction between some specific virion-bound host proteins with their natural cognate ligands present on target cells could mediate intracellular signaling cascade(s). For this purpose, we have generated a whole series of isogenic virus stocks (NL4-3 backbone) bearing or not bearing on their surface foreign CD28, CD54 (ICAM-1), CD80 (B7-1) or CD86 (B7-2) proteins. Our results indicate that incubation of human T lymphoid cells with virions bearing host-derived B7-2 proteins and anti-CD3 antibody can potently activate HIV-1 long terminal repeat-driven gene expression. This up-regulating effect necessitates the involvement of nuclear factor-kappa B (NF-kappa B) and nuclear factor of activated T cells (NFAT) as revealed by the use of vectors coding for dominant negative versions of both transcription factors (i.e. I kappa B alpha S32A/36A and dnNFAT) and band shift assays. The increase of NF-kappa B activity was abolished when infection with B7-2-bearing HIV-1 particles was performed in the presence of the fusion protein CTLA-4 Ig suggesting that the interaction between virally embedded B7-2 and CD28 on the target cell is responsible for the observed NF-kappa B induction. The findings presented here provide the first demonstration that host-encoded proteins acquired by HIV-1 can mediate signal transduction events.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Ste-Foy, Québec G1V 4G2, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Bounou
authors.forename: N
authors.initials: N
authors.lastname: Dumais
authors.forename: M J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014771:Virion / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha