PMID- 23291968
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20191210
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 25
IP  - 4
DP  - 2013 Apr
TI  - Glycodendrimers prevent HIV transmission via DC-SIGN on dendritic cells.
PG  - 221-33
LID - 10.1093/intimm/dxs115 [doi]
AB  - Dendritic cells (DCs) are antigen-presenting cells efficient in capturing 
      pathogens, and processing their antigenic determinants for presentation to 
      antigen-specific T cells to induce robust immune responses. Their location at 
      peripheral tissues and the expression of pattern-recognition receptors, among 
      them DC-specific intercellular adhesion molecule-3-grabbing non-integrin 
      (DC-SIGN), facilitates the capture of pathogens before spreading. However, some 
      pathogens have developed strategies to escape the immune system. One of the most 
      successful is HIV-1, which targets DC-SIGN for transport to the lymph node where 
      the virus infects CD4(+) T cells. Contact of HIV-1 with DC-SIGN is thus the first 
      event in the pathogenic cascade and, therefore, it is the primary target point 
      for therapies aimed at HIV infection prevention. DC-SIGN recognizes specific 
      glycans on HIV-1 and this interaction can be blocked by competitive inhibition 
      through glycans. Although the affinity of glycans is relatively low, multivalency 
      may increase avidity and the strength to compete with HIV-1 virions. We have 
      designed multivalent dendrimeric compounds based on Lewis-type antigens that bind 
      DC-SIGN with high selectivity and avidity and that effectively block gp120 
      binding to DC-SIGN and, consequently, HIV transmission to CD4(+) T cells. Binding 
      to DC-SIGN and gp120 inhibition was higher on glycodendrimers with larger 
      molecular diameter, indicating that the geometry of the compounds is an important 
      factor determining their functionality. Our compounds elicited DC-SIGN 
      internalization, a property of the receptor upon triggering, but did not affect 
      the maturation status of DCs. Thus, Le(X) glycodendrimers could be incorporated 
      into topic prophylactic approaches for the prevention of HIV-1 transmission.
FAU - Garcia-Vallejo, Juan J
AU  - Garcia-Vallejo JJ
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands.
FAU - Koning, Nathalie
AU  - Koning N
FAU - Ambrosini, Martino
AU  - Ambrosini M
FAU - Kalay, Hakan
AU  - Kalay H
FAU - Vuist, Ilona
AU  - Vuist I
FAU - Sarrami-Forooshani, Ramin
AU  - Sarrami-Forooshani R
FAU - Geijtenbeek, Teunis B H
AU  - Geijtenbeek TB
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130104
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Dendrimers)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lewis Blood Group Antigens)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Binding, Competitive
MH  - Cell Adhesion Molecules/agonists/*immunology
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Dendrimers/*chemistry
MH  - Dendritic Cells/drug effects/*immunology/virology
MH  - HIV Envelope Protein gp120/metabolism
MH  - HIV Infections/*prevention & control/*transmission
MH  - HIV-1/*immunology
MH  - Humans
MH  - Immune Evasion
MH  - Lectins, C-Type/agonists/*immunology
MH  - Lewis Blood Group Antigens/*chemistry
MH  - Molecular Targeted Therapy
MH  - Polysaccharides/agonists/chemical synthesis/*pharmacology
MH  - Receptors, Cell Surface/agonists/*immunology
MH  - Structure-Activity Relationship
MH  - Virus Internalization/drug effects
EDAT- 2013/01/08 06:00
MHDA- 2013/09/10 06:00
CRDT- 2013/01/08 06:00
PHST- 2013/01/08 06:00 [entrez]
PHST- 2013/01/08 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
AID - dxs115 [pii]
AID - 10.1093/intimm/dxs115 [doi]
PST - ppublish
SO  - Int Immunol. 2013 Apr;25(4):221-33. doi: 10.1093/intimm/dxs115. Epub 2013 Jan 4.