Immunologists refer to the cells that harbor HIV, even while someone is getting effective antiretroviral drugs, as the “reservoir.” That term inspires a lot of waterway metaphors! Unfortunately, drying up the HIV reservoir is not as straightforward as building a dam across a stream. But it is the goal, if we are talking about the still-elusive possibility of a HIV cure.

Maud Mavigner, Ann Chahroudi and colleagues at Yerkes recently published a paper in Journal of Virology on targeting the Wnt/beta-catenin pathway as a tactic. They were studying SIV-infected macaques, in the context of ongoing antiretroviral therapy.

The HIV reservoir is more difficult to visualize than a human-made aquatic reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo,the brain or the intestine. Beta-catenin is a central protein in that pathway.

In this case, Wnt/beta-catenin regulates the balance between self-renewal and differentiation of memory T cells – important components of the HIV reservoir. Mavigner’s team used PRI-724, a molecule that blocks interaction between beta-catenin and another protein it needs to turn on genes. PRI-724 has also been investigated in the context of cancer clinical trials.

The researchers were able to observe decreased proliferation of memory T cells and signs of more differentiation. However, short-term treatment with PRI-724 alone did not significantly reduce the size of the viral reservoir, they write. It is possible that PRI-724, or a similar drug, could be combined with other approaches for a longer time.

As the authors note, this was a shift away from the “shock and kill” approach that requires activating the dormant infected T cells as a way of bringing them out of the shadows: “A transient block to the proliferation of long-lived latently-infected memory CD4+ T-cells via selective inhibition of stem cell-like signaling pathways may represent a necessary and complementary approach to strategies directly targeting latent HIV.”