Nature and sequence of simian immunodeficiency virus-induced central nervous system lesions: a kinetic study

To determine the onsets and specificities of neuropathological features observed after simian immunodeficiency virus (SIV) infection of macaques, brains of 19 clinically unaffected rhesus monkeys (group A) were examined after intervals ranging from 1 to 48 weeks post-infection and compared to 8 animals with AIDS (group B) as well as to 8 uninfected controls. Based on morphological and virological parameters, seven patterns specific for SIV infection of the central nervous system (CNS) were discerned. In both groups of infected but not control animals, we found mononuclear aggregates in meninges, perivascular space, and choroid plexus stroma (designated pattern 1), isolated infected cells within CNS parenchyma (pattern 2), axonal degeneration (pattern 3), spongy change (pattern 4), microglial proliferation (pattern 5), and small vessel proliferation (pattern 6). SIV encephalitis (pattern 7) was only evident in animals with clinically evident disease. Changes characteristic of patterns 3, 5 and 6 appeared to be chronic and non-progressive, whereas lesions of patterns 1, 2 and 4 appeared to have progressed in animals with AIDS. The main component of mononuclear aggregates in animals of group A were lymphocytes, in contrast to animals of group B, in which macrophages dominated the inflammatory infiltrates. Altogether, our results demonstrate that subtle leukoencephalopathy was a specific feature of clinically silent as well as clinically evident phases of SIV infection. This might explain the neurological impairment of HIV-positive non-AIDS individuals.