Cells that harbor HIV, even while a person is on antiretroviral drugs, are referred to as the “reservoir”. Some of these cells might be able to self-renew/proliferate, thus continually replenishing the virus reservoir. The elusive task of “drying up” this reservoir is key in uncovering a cure.
Researchers at Yerkes National Primate Research Center (YNPRC) recently tested the possibility to block the reservoir self-renewal, working with macaques infected with SIV (Simian immunodeficiency virus) and targeting the Wnt/beta-catenin pathway during antiretroviral therapy.
Wnt is a common signaling pathway, and beta-catenin is a central protein in that pathway. Beta-catenin regulates the balance between self-renewal and differentiation (changing to another cell type, more mature and shorter-lived) of memory T cells.
The team used PRI-724, a molecule that blocks interaction between beta-catenin and another protein beta-catenin needs to turn on genes. The researchers noted decreased proliferation of long-lived memory T cells and signs of more differentiation into shorter-lived cells that are more prone to die. However, short-term treatment with PRI-724 alone didn’t significantly reduce the size of the overall viral reservoir.
The scientists noted, though, it may be possible PRI-724 or a similar drug could be combined with other approaches for a longer time to make a greater impact.
They also pointed out this technique differs from the “shock and kill” approach that activates dormant infected T cells to trigger an immune system response. NPRC scientists are testing this approach in separate, ongoing studies.