Relationship between viral load in blood, cerebrospinal fluid, brain tissue and isolated microglia with neurological disease in macaques infected with different strains of SIV

The role of the viral burden in the brain for the pathogenesis of human imm unodeficiency virus-associated neurological disorders is still unclear. To address this issue, we have quantified the viral load in plasma, cerebrospi nal fluid (CSF) and brain tissue of macaques infected with simian immunodef iciency virus (SIV). We discovered that the viral strain used for infection determines the replicative capacity in microglial cells as well as the ext ent of neuropathological lesions and the occurrence of neurological symptom s. Moreover, the viral load in the brain parenchyma correlated with the dev elopment of overt neurological disease whereas the one in plasma did not. B y comparing the viral load in three different compartments, we demonstrated that the viral burden in the CSF is influenced both by the viral replicati on in the periphery as well as in the brain parenchyma. According to these results, it is not the absolute amount of viral load in the CSF but rather the viral antigen contributed by the viral production within the brain whic h correlates with the development of neurological disease. In longitudinal studies, we observed that this autochthonous virus production, as evidenced by a ratio of the viral load in CSF to the one in plasma, takes place for a prolonged period of time before overt neurological signs are manifested. This finding suggests that this ratio could be used as a prognostic marker for immunodeficiency virus-induced neurological disease.