T cell activation is required for productive HIV-1 replication in primary T ceils. Therefore, we propose that essential processes and molecules required for H1V-1 replication become uniquely available to HIV-1during the activation of T cells. Currently, there is insufficient knowledge about the identity of host molecules employed during replication. To characterize host control factors we developed a novel intracellular peptide display technology that identifies dominant effector peptides capable of inhibiting HW-1 replication in T cells. Using this system we have obtained several peptides that inhibit the T cell activation processes on whichHIV-1 depends. These peptides will be used to determine the mechanism by which HIV-1 utilizes cellular resources. We expect that defined peptides will point to previously unidentified cellular processes required for HIV-1 replication, thus providing substantive information about intervention targets. We have already identified a target molecule for one of the four peptides. It is a known molecule involved in the regulation of T cell activation (details are provided in Preliminary Studies). In the present application, we propose to:1) Investigate the signaling pathway that includes this target molecule to determine its role in HIV-1replication and to understand why HIV-1 is able to take advantage of it.2) Initiate the identification of target molecules for the other inhibitor peptides to determine what other host factors are involved in HIV-1 replication processes. Findings from this project will allow us to characterize the biology of HIV-1 in human cells in greater detail and will provide new approaches to exploit molecular genetic intervention to understand and treat AIDS.
| Kinoshita, Shigemi M; Kogure, Amane; Taguchi, Shizuka et al. (2013) Snapin, positive regulator of stimulation- induced Ca²? release through RyR, is necessary for HIV-1 replication in T cells. PLoS One 8:e75297 |
| Kinoshita, Shigemi M; Krutzik, Peter O; Nolan, Garry P (2012) COP9 signalosome component JAB1/CSN5 is necessary for T cell signaling through LFA-1 and HIV-1 replication. PLoS One 7:e41725 |
