Objective To investigate the possible neurotropism, neuroinvasion and their mechanism in a Chinese-origin rhesus macaque infected with SIVmac251 showing neurological symptoms. MethodsEight healthy laboratory rhesus macaques were infected with SIVmac251-155p6N by intravenous injection. Among them 3 monkeys showed neurological symptoms to a different degree, and one of these 3 animals (R21755) developed severe neurological symptoms. This monkey was sacrificed and the virus was isolated from the basal ganglia of the brain, the plasma viral load was quantified by real-time RT-PCR, and T cell subsets were determined by flow cytometry. The brain lesions were examined by histopathology using HE staining. The RNAs were extracted from SIVmac251-155p6N, plasma and basal ganglia, the gp120 genes were amplified with single genome amplification, and the changes of N-glycosylation site in gp120 regions were analyzed. ResultsThe monkey R21755 presented AIDS encephalopathy-like symptoms after half a year post the viral infection. Pathological examination showed infiltration of macrophages and multinucleated giant cells in perivascular space, and degeneration and necrosis of neurons were observed in the brain tissue. The gp120 sequence analysis showed that the virus isolated from the brain was partly different from that of the other sequences of SIVmac251-155p6N and plasma virus of the monkey R21755. The variations were mainly in the V1/V4 regions and the loss of a N-glycosylation site in env C1. ConclusionsIt seems that the neuroinvasion and neurovirulence of SIVmac251 are significantly enhanced during the long-term adaption in vivo. The finding of this study provide a firm molecular basis for establishing a strain of SIVmac251 with neurotropism and neurovirulence. This would be very meaningful for investigating the role of SIV in neurologic disease and studies of AIDS neuropathy. 