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

Human immunodeficiency virus (HIV) infection leads to clinically significan t neuronal pathology, but the underlying mechanism remains unclear. Infecti on 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 SIVmac 251 (n = 22), HIV-2 (n = 6), SIVmac239 (n = 7) and poliovirus (n = 10) were investigated, together with 16 controls. Hippocampal pyramidal cell diamet er, averaged across the four CA subfields, was reduced by 16.6% in the SIVm ac251 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, Convers ely, SIVmac239, which does cause immunosuppression, caused an average neuro nal 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 neurovirulen ce testing acted as positive controls for CNS inflammation and they also sh owed an increase in neuronal diameter (4.1%, P = 0.025). The atrophy seen w ith SIVmac251 and HIV-2 involved all CA subfields but the hypertrophy follo wing SIVmac239 or poliovirus infection was restricted to CA1 and CA2. These observations show a dissociation between the ability of immunodeficiency v iruses to cause immune suppression and neuronal pathology and demonstrate t hat CNS inflammation per se may cause neuronal hypertrophy.