Endocytosis of human immunodeficiency virus 1 (HIV-1) in astrocytes: A fiery path to its destination

• HIV-1 infection in astrocytes is impeded at the viral entry level.
• Astrocytes adsorb HIV-1 particles and release them within 10 days.
• HIV-1 infects astrocytes minimally by pH-dependent endocytosis.
• Inhibiting endosomal acidification or increasing endosomal pH by lysosomotropic agents, bolstered both M- and T-tropic HIV-1.

Despite successful suppression of peripheral HIV-1 infection by combination antiretroviral therapy, immune activation by residual virus in the brain leads to HIV-associated neurocognitive disorders (HAND). In the brain, several types of cells, including microglia, perivascular macrophage, and astrocytes have been reported to be infected by HIV-1. Astrocytes, the most abundant cells in the brain, maintain homeostasis. The general consensus on HIV-1 infection in astrocytes is that it produces unproductive viral infection. HIV-1 enters astrocytes by pH-dependent endocytosis, leading to degradation of the virus in endosomes, but barely succeeds in infection. Here, we have discussed endocytosis-mediated HIV-1 entry and viral programming in astrocytes.