Long-lived latently infected cells present a major obstacle to curing HIV infection; however, the upstream
biochemical processes and signal transduction events that favor active HIV replication versus latent infection are
poorly understood. We hypothesize that quality of signals at the time of infection is critical for establishing HIV
latency. To investigate how signals contribute to productive or latent HIV infection we will use chimeric antigen
receptors to modulate signaling at the time of infection. In addition, we will explore the cross talk between T cell
receptor signaling cascades and those delivered across the virological synapse during cell-cell transmission of
HIV. We are proposing the following three specific aims: 1) how does differential signaling influence HIV-1
infection of T cells; 2) identifying signaling events that are required for HIV infection; and 3) determine whether
antigen receptor signal strength at the virological synapse influences HIV infection. In addition to the hypothesis,
innovative aspects of this proposal include the interdisciplinary approach, which uses cellular, molecular and
bioengineering tools to identify key regulatory networks that influence HIV infection. These studies will provide
new insights into key regulatory networks that govern the establishment of HIV infection and latency.
Furthermore, understanding the minimal requirements for T cell signaling and HIV infection will potentially identify
novel cellular targets which could be manipulated in an effort to alter the size of the latent reservoir and the
course of HIV/AIDS progression.