title: CD4 binding affinity determines human immunodeficiency virus type 1-induced alpha interferon production in plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (PDC) are major producers of type I interferons (IFN) in response to human immunodeficiency virus type 1 (HIV-1) infection. To better define the underlying mechanisms, we studied the magnitude of alpha IFN (IFN-alpha) induction by recombinant viruses containing changes in the Env protein that impair or disrupt CD4 binding or expressing primary env alleles with differential coreceptor tropism. We found that the CD4 binding affinity but not the viral coreceptor usage is critical for the attachment of autofluorescing HIV-1 to PDC and for subsequent IFN-alpha induction. Our results illustrate the importance of the gp120-CD4 interaction in determining HIV-1-induced immune stimulation via IFN-alpha production.
authors.affiliation: German National Reference Centre for Retroviruses, Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Haupt
authors.forename: Norbert
authors.initials: N
authors.lastname: Donhauser
authors.forename: Chawaree
authors.initials: C
authors.lastname: Chaipan
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuster
authors.forename: Bridget
authors.initials: B
authors.lastname: Puffer
authors.forename: Rod S
authors.initials: RS
authors.lastname: Daniels
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Greenough
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D003713:Dendritic Cells / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007668:Kidney / Q000166:cytology; D008875:Middle Aged; D014162:Transfection; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D016898:Interferon-alpha