PUBLICATION
HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium
- Authors
- Urbinati, C., Nicoli, S., Giacca, M., David, G., Fiorentini, S., Caruso, A., Alfano, M., Cassetta, L., Presta, M., and Rusnati, M.
- ID
- ZDB-PUB-090814-2
- Date
- 2009
- Source
- Blood 114(15): 3335-3342 (Journal)
- Registered Authors
- Presta, Marco
- Keywords
- none
- MeSH Terms
-
- Animals
- Cattle
- Cell Adhesion
- Cell Line, Tumor
- Cell Movement*
- Chemokine CCL5/pharmacology
- Chemokine CXCL12/pharmacology
- Embryo, Nonmammalian/metabolism
- Endothelium, Vascular/metabolism*
- HIV Infections/genetics
- HIV Infections/metabolism*
- HIV-1/metabolism*
- Heparan Sulfate Proteoglycans
- Humans
- Lymphocytes/metabolism*
- Protein Multimerization
- Syndecan-1
- Transfection
- Zebrafish/genetics
- Zebrafish/metabolism
- tat Gene Products, Human Immunodeficiency Virus/genetics
- tat Gene Products, Human Immunodeficiency Virus/metabolism*
- PubMed
- 19661268 Full text @ Blood
Citation
Urbinati, C., Nicoli, S., Giacca, M., David, G., Fiorentini, S., Caruso, A., Alfano, M., Cassetta, L., Presta, M., and Rusnati, M. (2009) HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium. Blood. 114(15):3335-3342.
Abstract
The HIV transactivating factor Tat accumulates on the surface of endothelium by interacting with heparan sulfate proteoglycans (HSPGs). Tat also interacts with B-lymphoid Namalwa cells but only when these overexpress HSPGs following syndecan-1 cDNA transfection (SYN-NCs). Accordingly, SYN-NCs, but not mock-transfected cells, adhere to endothelial cells (ECs) when Tat is bound to the surface of either one of the two cell types or when SYN-NCs are transfected with a Tat cDNA. Moreover, endogenously produced Tat bound to cell-surface HSPGs mediates cell adhesion of HIV+ ACH-2 lymphocytes to the endothelium. This heterotypic lymphocyte-EC interaction is prevented by HSPG-antagonists or heparinases treatment, but not by integrin-antagonists and requires the homodimerization of Tat protein. Tat tethered to the surface of SYN-NCs or of peripheral blood monocytes from healthy donors promotes their transendothelial migration in vitro in response to CXCL12 or CCL5, respectively, and SYN-NCs extravasation in vivo in a Zebrafish embryo model of inflammation. In conclusion, Tat homodimers bind simultaneously to HSPGs expressed on lymphoid and EC surfaces, leading to HSPG/Tat-Tat/HSPG quaternary complexes that physically link HSPG-bearing lymphoid cells to the endothelium, promoting their extravasation. These data provide new insights about how lymphoid cells extravasate during HIV infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping