Endogenous HIV-1 Tat Promotes Cell Proliferation, Migration, and Phagocytosis in Stably Infected Macrophages by Accumulating Lactate and Activating the Autophagy/MAPK Pathway.

HIV-1 infection remains difficult to treat due to the virus's ability to persist in host cells such as memory CD4+ T cells and peripheral macrophages. Tat, an HIV-1 regulatory protein, also modulates transcription in host cells. However, the mechanisms by which Tat stably affects macrophage functions, critical host cells for HIV-1, remain unclear. This study demonstrates that Tat promotes macrophage proliferation, migration, and phagocytosis. In-depth analysis reveals that HIV-1 Tat enhances lactate accumulation, induces reactive oxygen species (ROS), and activates the MAPK pathway in macrophages. Additionally, lactate induces autophagy activation, leading to increased levels of Arg1 and TGF-β, which drive phagocytosis and migration, respectively. By examining the activity of macrophages stably infected with Tat, this study provides new insights into Tat's latent influence on macrophage function, offering theoretical support for understanding HIV-1 infection mechanisms.