Project Grant R01MH143137

The National Institute of Mental Health awarded The Trustees of The University of Pennsylvania $1,217,055 on July 17, 2026, under the Mental Health Research Grants program (CFDA 93.242) to investigate selective inhibition of T cell trafficking to the brain during acute SHIV infection in rhesus macaques.

The research leverages a validated nonhuman primate model of HIV neuropathogenesis and persistence to determine how blocking T cell circulation during acute SHIV.D infection affects the establishment of durable brain viral reservoirs. The study will characterize the role of CD4+ T cells in CNS reservoir seeding, viral persistence, and neuropathogenesis—gaps in understanding that remain despite prior characterization of myeloid cells as primary CNS HIV reservoirs on long-term suppressive antiretroviral therapy. The work uses genetically barcoded SHIV.D, a CCR5-tropic virus that efficiently replicates in both CD4+ T cells and macrophages and consistently infects the CNS, causes neuroinflammation, and persists through ART via long-lived myeloid reservoirs. The team will apply FTY720, a clinically approved immunomodulating therapy for multiple sclerosis, to induce rapid redistribution of CD4+ T cells from blood into peripheral tissues while preserving blood monocyte migration, enabling dissection of T cell-specific roles in CNS persistence and neuroinflammation. Performance takes place at the University of Pennsylvania in Philadelphia, Pennsylvania. The period of performance runs through March 31, 2031. This is a Project Grant, the standard investigator-initiated research award under NIMH's grant portfolio.