Changes in neuron size in cynomolgus macaques infected with various immunodeficiency viruses and poliovirus

Human immunodeficiency virus (HIV) infection leads to clinically significant neuronal pathology, but the underlying mechanism remains unclear. Infection of rhesus macaques with the simian immunodeficiency virus SIVmac251 has been shown to cause atrophy of hippocampal pyramidal cells. The aim of the current investigation was to determine whether SIVmac251 and other viruses with differing abilities to cause immune suppression or encephalitis could cause neuronal atrophy in cynomolgus macaques. Animals infected with SIVmac251 (n = 22), HIV-2 (n = 6). SIVmac239 (n = 7) and poliovirus (n = 10) were investigated, together with 16 controls. Hippocampal pyramidal cell diameter, averaged across the four CA subfields, was reduced by 16.6% in the SIVmac251 group (P < 0.0001) and by 13.3% in the HIV-2 group (P < 0.001), even though the latter virus does not generally cause immunosuppression. Conversely, SIVmac239, which does cause immunosuppression, caused an average neuronal hypertrophy of 6.8% (P = 0.033). Of possible relevance to the different behaviour of the two SIVs is that SIVmac239 is lymphocyte tropic and does not infect CNS microglia in vivo whereas SIVmac251 does. Animals inoculated with poliovirus into the lumbar spinal cord for polio vaccine neurovirulence testing acted as positive controls for CNS inflammation and they also showed an increase in neuronal diameter (4.1%, P = 0.025). The atrophy seen with SIVmac251 and HIV-2 involved all CA subfields but the hypertrophy following SIVmac239 or poliovirus infection was restricted to CA1 and CA2. These observations show a dissociation between the ability of immunodeficiency viruses to cause immune suppression and neuronal pathology and demonstrate that CNS inflammation per se may cause neuronal hypertrophy.