Novembre F J, De Rosayro J, O'Neil S P, Anderson D C, Klumpp S A, McClure H M
Divisions of Microbiology and Immunology, Yerkes Regional Primate Research Center, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
J Virol. 1998 Nov;72(11):8841-51. doi: 10.1128/JVI.72.11.8841-8851.1998.
Transfusion of blood from a simian immunodeficiency virus (SIV)- and simian T-cell lymphotropic virus-infected sooty mangabey (designated FGb) to rhesus and pig-tailed macaques resulted in the development of neurologic disease in addition to AIDS. To investigate the role of SIV in neurologic disease, virus was isolated from a lymph node of a pig-tailed macaque (designated PGm) and the cerebrospinal fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques. SIV-related neuropathogenic effects were observed in 100% of the pig-tailed macaques inoculated with either virus. Lesions in these animals included extensive formation of SIV RNA-positive giant cells in the brain parenchyma and meninges. Based upon morphology, the majority of infected cells in both lymphoid and brain tissue appeared to be of macrophage lineage. The virus isolates replicated very well in pig-tailed and rhesus macaque peripheral blood mononuclear cells (PBMC) with rapid kinetics. Differential replicative abilities were observed in both PBMC and macrophage populations, with viruses growing to higher titers in pig-tailed macaque cells than in rhesus macaque cells. An infectious molecular clone of virus derived from the isolate from macaque PGm (PGm5.3) was generated and was shown to have in vitro replication characteristics similar to those of the uncloned virus stock. While molecular analyses of this virus revealed its similarity to SIV isolates from sooty mangabeys, significant amino acid differences in Env and Nef were observed. This virus should provide an excellent system for investigating the mechanism of lentivirus-induced neurologic disease.
将来自感染猿猴免疫缺陷病毒（SIV）和猿猴T细胞嗜淋巴细胞病毒的乌黑白眉猴（命名为FGb）的血液输注给恒河猴和豚尾猕猴，除了导致艾滋病外，还引发了神经疾病。为了研究SIV在神经疾病中的作用，从一只豚尾猕猴（命名为PGm）的淋巴结和一只恒河猴（命名为ROn2）的脑脊液中分离出病毒，并将其接种到其他猕猴体内。在接种了任何一种病毒的豚尾猕猴中，100%都观察到了与SIV相关的神经致病作用。这些动物的病变包括脑实质和脑膜中广泛形成SIV RNA阳性巨细胞。根据形态学，淋巴组织和脑组织中大多数受感染细胞似乎是巨噬细胞谱系。病毒分离株在豚尾猕猴和恒河猴外周血单个核细胞（PBMC）中复制良好，动力学很快。在PBMC和巨噬细胞群体中观察到不同的复制能力，病毒在豚尾猕猴细胞中的滴度高于在恒河猴细胞中的滴度。从猕猴PGm分离株（PGm5.3）衍生出一种病毒感染性分子克隆，其体外复制特性与未克隆的病毒毒株相似。虽然对这种病毒的分子分析显示它与来自乌黑白眉猴的SIV分离株相似，但在Env和Nef中观察到了显著的氨基酸差异。这种病毒应该为研究慢病毒诱导神经疾病的机制提供一个极好的系统。
