Eradication of human immunodeficiency virus from brain reservoirs

Abstract

Isolated cases in which human immunodeficiency virus (HIV) infection was claimed to have been eradicated generated renewed interest in HIV reservoirs in the brain particularly since attempts to reproduce the findings using genetically engineered stem cells and immune- or myeloablation have failed. A clear understanding of the cell types in which the virus resides in the brain, the mechanism of viral persistence, restricted replication and latency, and the turnover rate of the infected cells is critical for us to develop ways to control or get rid of the virus in the brain. The brain has several unique features compared to other reservoirs. There are no resident T cells in the brain; the virus resides in macrophages and astrocytes where the viral infection is non-cytopathic. The virus evolves in the brain and since the turnover rate of these cells is low, the virus has the potential to reside in these cells for several decades and possibly for the life of the individual. This review discusses the HIV reservoirs in the brain, issues related to eradication of the virus from sanctuaries in the brain, and current challenges faced by neuroscientists in finding a cure.

Sites of HIV Reservoir in the Brain: HIV in compartmentalized in the subcortical white matter and the midline structures of the brain. This includes the frontal and temporal lobe, the basal ganglia and the brain stem. The posterior parts of the brain are relatively spared. Within these regions HIV infects the macrophages/microglia and astrocytes most commonly located in the perivascular regions where they constitute the blood brain barrier. A previously under appreciated site of viral infection in the brain is the subarachnoid space where the meningeal macrophages form a rich plexus of cells surrounding the meningeal blood vessels. Viral sequencing suggests that the meninges harbor both brain and peripheral blood derived viruses, suggesting that this may be a route for viral transmission from brain to blood. Alternatively, the virus can spread along the meningeal macrophages to the brain parenchyma