Macrophages: a crucial reservoir for human immunodeficiency virus in the body

The replication of Human Immunodeficiency Virus (HIV) in cells of macrophag e lineage represents a key pathogenetic event of the neurological damages t ypically found during the course of this disease. Macrophages are persistently infected cells and thus not susceptible to the cytophatic effect typical of infected activated CD4-lymphocytes. The resis tance of macrophages to HIV infection is at least in part mediated by the a utocrine production of the nerve growth factor (NGF), a neurokine able to s ustain the survival of some cells of bone marrow origin, including monocyte -derived macrophages. This anti-apoptotic effect of NGF in HIV-Infected mac rophages can be even more relevant at the central nervous system level, whe re many cells are able to physiologically produce NGF, thus further increas ing the survival of macrophages infected by HIV, and enhancing the damages that these cells may induce upon bystander neurons. The proapoptotic effect of soluble factors released by HIV-infected macrophages may heavily affect the survival and functions also of astrocytes, that in turn become unable to sustain neuronal homeostasis. Taken together, this information supports the importance of therapeutic attempts aimed at attacking virus replication in infected macrophages and/or to selectively eliminate these chronically infected and persistently virus-producing cells.