Identification of Signals Required for the Establishment of HIV Infection and Latency

Boston Medical Center, Boston MA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): 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, nanoparticles that target the virological synapse will be employed to interrogate how the strength of T cell receptor signaling impacts cell-cell transmission of HIV. We are proposing the following three specific aims: 1) how does differential signaling influence HIV-1 infection of cells; 2) determine whether antigen receptor signal strength at the virological synapse influences HIV infection; and 3) identifying signaling events that are required for HIV infection. n addition to the hypothesis, innovative aspects of this proposal include the interdisciplinary approach, which uses cellular, molecular, bioengineering and nanotechnology 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 persistence. 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 sie of the latent reservoir and the course of HIV/AIDS progression.