HIV envelope gp120 alters T-cell receptor mobilization in the immunological synapse of uninfected CD4 T cells and augments the T cell activation

HIV is transmitted most efficiently from cell to cell and productive infection occurs mainly in activated CD4 T cells. It is postulated that HIV exploits immunological synapses formed between CD4 T cells and antigen-presenting cells to facilitate the targeting and infection of activated CD4 T cells. This study sought to evaluate how the presence of the HIV envelope (Env) in the CD4 T cell immunological synapse affects synapse formation and intracellular signaling to impact the downstream T cell activation events. CD4 T cells were applied onto supported lipid bilayers (SLBs) that were reconstituted with HIV Env gp120, anti-TCR antibody OKT3 and ICAM-1 to represent the surface of HIV Env-bearing antigen-presenting cells. The results showed that the HIV Env did not disrupt immunological synapse formation. Instead, the HIV Env accumulated with TCR at the center of the synapse, altered the kinetics of TCR recruitment to the synapse, and affected the synapse morphology over time. The HIV Env also prolonged Lck phosphorylation at the synapse and enhanced TCR-induced CD69 upregulation, IL-2 secretion, and proliferation to promote virus infection. These results suggest that HIV uses the immunological synapse as a conduit not only for selective virus transmission to activated CD4 T cells, but also for boosting the T cell activation state, thereby increasing its likelihood for undergoing productive replication in the targeted CD4 T cells.There are about two million new HIV infections every year. A better understanding on how HIV is transmitted to the susceptible cells is critical to devise effective strategies to prevent HIV infection. Activated CD4 T cells are preferentially infected by HIV, although how this is accomplished is not fully understood. This study examined whether HIV co-opts the normal T-cell activation process through the so-called immunological synapse. We found that the HIV envelope is recruited to the center of the immunological synapse together with the T-cell receptor and enhances the T cell receptor-induced activation of the CD4 T cells. The heightened cellular activation promotes the capacity of the CD4 T cells to support productive HIV replication. This study provides evidence for the exploitation of the normal immunological synapse and T-cell activation process by HIV to boost the activation state of the targeted CD4 T cells and promote infection of these cells