Role of microglia in SIV-induced encephalopathy
Project management at the University of Würzburg:
HIV infects the central nervous system (CNS) and induces neurological deficiencies in a great proportion of HIV-patients. Infection of neural cells is surely a prerequisite for the induction of this neurological disease. However, it is still not clear, whether the level of the intrathecal viral replication is strictly correlated with the extent of neurological symptoms. In addition, not neurons but microglia cells are the primary target for a productive infection. Therefore, indirect mechanisms have to be responsible for the observed neurodegeneration in AIDS-patients. We have used the infection of rhesus monkeys with simian immunodeficiency viruses (SIV) as animal model in order to study the viral replication and the production of potentially neurotoxic substances by microglial cells, in more detail. We could demonstrate that the viral replication in the CNS is influenced by both virological and immunological factors. According to our results, only macrophage tropic viruses are able to efficiently replicate in microglia. A comparison of the viral load in the cerebrospinal fluid with the one in plasma can be used as a diagnostic marker for the parenchymal viral load. Using this parameter, we could show that a strong intrathekal replication must take place for a prolonged period of time until the animals develop neuropathological lesions and overt neurological signs. Infected as well as uninfected microglial cells are increasingly activated during the course of the disease. This leads to production of potentially neurotoxic substances. For example, we demonstrated an increased production of the excitotoxic amino acid glutamate.
Projekt period: from 01.1999 to 12.2001