Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells.
The establishment of HIV type 1 (HIV-1) infection is initiated by the stable attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between virus-encoded gp120 and cell surface CD4, a number of distinct interactions influence binding of HIV-1 to host cells. In this study, we report that galectin-1, a dimeric beta-galactoside-binding protein, promotes infection with R5, X4, and R5X4 variants. Galectin-1 acts as a soluble adhesion molecule by facilitating attachment of HIV-1 to the cell surface. This postulate is based on experiments where galectin-1 rendered HIV-1 particles more refractory to various agents that block HIV-1 adsorption and coreceptor binding (i.e., a blocking anti-CD4, soluble CD4, human anti-HIV-1 polyclonal Abs; stromal cell-derived factor-1alpha; RANTES). Experiments performed with the fusion inhibitor T-20 confirmed that galectin-1 is primarily affecting HIV-1 attachment. The relevance of the present findings for the pathogenesis of HIV-1 infection is provided by the fact that galectin-1 is abundantly expressed in the thymus and lymph nodes, organs that represent major reservoirs for HIV-1. Moreover, galectin-1 is secreted by activated CD8(+) T lymphocytes, which are found in high numbers in HIV-1-positive patients. Therefore, it is proposed that galectin-1, which is released in an exocrine fashion at HIV-1 replication sites, can cross-link HIV-1 and target cells and promote a firmer adhesion of the virus to the cell surface, thereby augmenting the efficiency of the infection process. Overall, our findings suggest that galectin-1 might affect the pathogenesis of HIV-1 infection.
Ouellet
Michel
M
Laboratory of Human Immuno-Retrovirology, Research Center in Infectious Diseases, Centre Hospitalier de l'Université Laval, and Faculty of Medicine, Laval University, Quebec, Canada.
Mercier
Simon
S
Pelletier
Isabelle
I
Bounou
Salim
S
Roy
Jocelyn
J
Hirabayashi
Jun
J
Sato
Sachiko
S
Tremblay
Michel J
MJ
D001685:Biological Factors; D002448:Cell Adhesion; D002478:Cells, Cultured; D037483:Galectin 1 / Q000031:analogs & derivatives* / Q000502:physiology*; D037502:Galectin 3; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D011485:Protein Binding; D012995:Solubility; D014018:Tissue Distribution
D001685:Biological Factors; D037483:Galectin 1; D037502:Galectin 3; C445499:LGALS1 protein, human