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Interaction of HIV‐1 with dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin‐expressing cells is influenced by gp120 envelope modifications associated with disease progression
Author(s) -
Nabatov Alexey A.,
van Montfort Thijs,
Geijtenbeek Teunis B. H.,
Pollakis Georgios,
Paxton William A.
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05491.x
Subject(s) - biology , microbiology and biotechnology , dc sign , dendritic cell , cell adhesion molecule , cell adhesion , cell , antigen , immunology , genetics
Dendritic cells can enhance the replication of HIV‐1 in CD4 + lymphocytes through the interaction of the gp120 envelope protein with such molecules as dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin. The variable loops of gp120 have previously been shown to modulate the interaction of HIV‐1 with its principal receptor CD4 and its various coreceptors, namely CCR5 and CXCR4. Here, we utilized a panel of molecular cloned viruses to identify whether gp120 modifications can influence the virus interaction with immature dendritic cells or a cell line expressing dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin (Raji‐DC‐SIGN). The viruses encompass the R5, R5X4 and X4 phenotypes, and are based upon V1V2 and V3 sequences from a patient with disease progression. We found that dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin enhancement of virus replication can be modulated by the V1V2 length, the overall V3 charge and N‐linked glycosylation patterns; similar results were observed with immature dendritic cells. Viruses with higher V3 charges are more readily transferred to CD4 + lymphocytes when the V1V2 region is longer and contains an additional N‐linked glycosylation site, whereas transfer of viruses with lower V3 charges is greater when the V1V2 region is shorter. Viruses differing in the V1V2 and V3 regions also demonstrated differential capture by Raji‐DC‐SIGN cells in the presence of mannan. These results indicate that the interaction between HIV‐1 and immature dendritic cells via such molecules as dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin may have a role in selecting viruses undergoing transmission and evolution during disease progression.