CD4 binding affinity determines human immunodeficiency virus type 1-induced alpha interferon production in plasmacytoid dendritic cells.
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.
Haupt
Sabrina
S
German National Reference Centre for Retroviruses, Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen, Germany.
Donhauser
Norbert
N
Chaipan
Chawaree
C
Schuster
Philipp
P
Puffer
Bridget
B
Daniels
Rod S
RS
Greenough
Thomas C
TC
Kirchhoff
Frank
F
Schmidt
Barbara
B
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
D015704:CD4 Antigens; D016898:Interferon-alpha