HIV Entry Into Renal Tubular Epithelial Cells Through Cell–Cell Adhesion

Using live confocal imaging, Chen et al followed interactions between renal tubular epithelial cells (RTECs) and co-cultured fluorescently-tagged-HIV infected CD4+ T cells and recently demonstrated that the viral RNA was directly transferred from the infected CD4+ T cells into RTECs. The virus transfer required cell surface heparin sulfate proteoglycans (which serve as attachment receptors for HIV-1 on macrophages and dendritic cells) and stable cell–cell adhesion and was independent of HIV Env expression. Interestingly, the quantity of viral RNA transferred through cell–cell adhesion was much higher than that achieved by exposure large amounts of cell-free virus.

The authors also demonstrated that the HIV virus acquired via cell–cell contact results in de novo synthesis of viral proteins in the infected RTECs. Furthermore, reverse transcriptase, protease and integrase inhibitors seem to block gene expression in the RTECs that acquired the infection from cell-free virus but not in the RTECs that acquired the virus via cell–cell contact.

In summary, it seems that direct transfer of virus from infected T cells to RTECs is possible in vitro on cell–cell contact via a highly efficient mechanism that is independent of Env. The extent to which this happens in vivo and contributes to the pathogenesis of HIV-associated nephropathy remains to be seen.

Reference: chen et al. J Am Soc Nephrol. 2011 Mar;22(3):496-507. Epub 2011 Feb 18.