Addition of a single gp120 glycan confers increased binding to dendritic cell-specific ICAM-3-grabbing nonintegrin and neutralization escape to human immunodeficiency virus type 1.
The potential role of dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) binding in human immunodeficiency virus transmission across the mucosal barrier was investigated by assessing the ability of simian-human immunodeficiency chimeric viruses (SHIVs) showing varying degrees of mucosal transmissibility to bind the DC-SIGN expressed on the surface of transfected cells. We found that gp120 of the highly transmissible, pathogenic CCR5-tropic SHIV(SF162P3) bound human and rhesus DC-SIGN with an efficiency threefold or greater than that of gp120 of the nonpathogenic, poorly transmissible parental SHIV(SF162), and this increase in binding to the DC-SIGN of the SHIV(SF162P3) envelope gp120 translated into an enhancement of T-cell infection in trans. The presence of an additional glycan at the N-terminal base of the V2 loop of SHIV(SF162P3) gp120 compared to that of the parental virus was shown to be responsible for the increase in binding to DC-SIGN. Interestingly, this glycan also conferred escape from autologous neutralization, raising the possibility that the modification occurred as a result of immune selection. Our data suggest that more-efficient binding of envelope gp120 to DC-SIGN could be relevant to the enhanced mucosal transmissibility of SHIV(SF162P3) compared to that of parental SHIV(SF162).
Lue
James
J
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Hsu
Mayla
M
Yang
David
D
Marx
Preston
P
Chen
Zhiwei
Z
Cheng-Mayer
Cecilia
C
D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D015815:Cell Adhesion Molecules; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016023:Integrins; D009500:Neutralization Tests; D011134:Polysaccharides / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; C483616:ICAM3 protein, human; D016023:Integrins; D011134:Polysaccharides