WFDC1 expression identifies memory CD4 T lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions

This study investigates the role of the whey acidic protein (ps20), a member of the WFDC1 family, in promoting HIV-1 transmission between CD4+ T cells, specifically through enhancing intercellular adhesion. The research demonstrates that ps20 expression increases the susceptibility of T cells to HIV-1 infection by facilitating the formation of stable conjugates between HIV-infected and uninfected T cells, leading to efficient virus transfer.

Key findings:

1. Ps20 Enhances Cell-Cell HIV-1 Transfer: High levels of ps20 on CD4+ T cells correlate with increased HIV-1 transfer, both in Jurkat cells and primary T cell clones. Ps20 enhances virological synapse formation, enabling efficient cell-cell HIV-1 transmission.

   
   

2. ICAM-1 Modulation: Ps20 promotes HIV-1 transfer by modulating the expression of ICAM-1, an adhesion molecule crucial for T cell conjugate formation. Knockdown of ps20 reduces both ICAM-1 expression and HIV-1 transfer, while recombinant ps20 enhances the process.

   
   

3. Increased Conjugate Formation: Cells with high ps20 expression form more conjugates and multiple conjugates (polysynapses) with HIV-1-infected cells, facilitating viral spread.

   
   

4. Fusion-Dependent HIV-1 Transfer: The study also confirms that ps20-driven HIV-1 transfer is fusion-dependent, highlighting its role in productive infection.

   
   

In conclusion, ps20 is identified as a key factor in promoting HIV-1 dissemination between T cells, making ps20 a novel target for understanding HIV-1 pathogenesis and potential therapeutic intervention. This work provides new insights into the molecular mechanisms that enhance HIV-1 spread in vivo, particularly through promoting T cell conjugation and virological synapse formation.

https://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-8-29