Open AccessCD4 Binding Affinity Determines Human Immunodeficiency Virus Type 1-Induced Alpha Interferon Production in Plasmacytoid Dendritic Cells
Author(s) -
Sabrina Haupt,
Norbert Donhauser,
Chawaree Chaipan,
Philipp Schuster,
Bridget A. Puffer,
Rod S. Daniels,
Thomas C. Greenough,
Frank Kirchhoff,
Bárbara Schmidt
Publication year - 2008
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00196-08
Subject(s) - biology , tropism , virology , interferon , alpha interferon , recombinant dna , virus , interferon type i , immune system , plasmacytoid dendritic cell , dendritic cell , immunology , gene , genetics
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-α) induction by recombinant viruses containing changes in the Env protein that impair or disrupt CD4 binding or expressing primaryenv 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-α induction. Our results illustrate the importance of the gp120-CD4 interaction in determining HIV-1-induced immune stimulation via IFN-α production.