Background:  Cell-to-cell transmission is an efficient way retroviruses use to infect CD4⁺ T cells. HIV-1 exploits immune cell communications such as dendritic cells (DC) and macrophages CD4⁺ T lymphocytes to achieve a more efficient viral spread. Endothelial cells interact also with CD4⁺ T cells during their passages into the blood. However, the involvement of this type of interaction in HIV-1 propagation remains poorly defined. HIV-1 incorporates a variety of host-derived proteins, including the L-selectin CD62L, during its budding process. CD62L participates in the immune response by allowing rolling of leukocytes during the process of transmigration. Endothelial cells expressed various ligands of CD62L, such as E-selectin, MadCam-1, GlyCAM-1, PCLP, and sgp200. Considering the natural role of L-selectin and its presence onto HIV-1 virions, we postulated that CD62L-carrying virions might be more efficiently transferred from endothelial cells to CD4⁺ T cells.

Methods:  Human umbilical vein endothelial cells (HUVEC) and CD4⁺ T cells were isolated from different healthy donors. Virions either lacking or bearing host CD62L were generated by calcium phosphate co-precipitation in 293T cells. The extent of virus binding was assessed by measuring the p24 content, whereas virus transfer between endothelial and CD4⁺ T cells was evaluated by measuring p24 in cell-free supernatants at various days after co-culture.

Results:  We found that viruses bearing host-derived CD62L bind more with more efficiency to endothelial cells than viruses lacking this host protein. Moreover, infection in trans was also increased when using CD62L-bearing viruses. Interestingly, the effect of CD62L on both viral binding and transfer was abolished upon treatment of virions with a blocking antibody, but not with a control isotype-matched antibody.

Conclusions:  Taken together, these results suggest that CD62L play an important role in attachment of HIV-1 particles to endothelial cells, a phenomenon linked to a better HIV-1 transfer toward CD4⁺ T lymphocytes. Additional work is needed to shed light on the CD62 ligand(s) responsible for the observed phenomenon and also to define whether other step(s) in virus life cycle can be affected upon acquisition of CD62L. These observations confirm that host-derived proteins located on the exterior of HIV-1 can modulate the biology of this retrovirus.