Zink M C, Amedee A M, Mankowski J L, Craig L, Didier P, Carter D L, Muñoz A, Murphey-Corb M, Clements J E
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Am J Pathol. 1997 Sep;151(3):793-803.
To investigate the viral and host factors that contribute to neurological disease, nine macaques were intravenously co-inoculated with SIV/DeltaB670, a primary isolate of SIV consisting of at least 21 different genotypes, and SIV/17E-Fr, a neurovirulent recombinant clone. CD4+ cell counts and antigenemia were measured throughout infection. The SIV env V1 region was amplified from brain and peripheral blood mononuclear cell DNA to compare the genotypes present in brain and blood. Seven of the 9 macaques (78%) developed typical SIV-associated neurological lesions classified as severe (4 macaques), moderate (2 macaques), or mild (1 macaque) with a mean time to euthanasia of 7 months. Macaques with severe neurological lesions progressed more rapidly, with a mean time to euthanasia of 3-6 months. SIV/17E-Fr was detected in brain homogenates from all four macaques with severe encephalitis, and in three of the four, SIV/17E-Fr was the only genotype identified in the central nervous system. Macaques with less severe or no neurological lesions usually had one of various genotypes of SIV/DeltaB670 in brain. A variety of genotypes of SIV/DeltaB670 and SIV/17E-Fr were detected in peripheral blood mononuclear cells throughout infection. Macaques with severe neurological lesions had the most precipitous declines in CD4+ cell counts, the highest levels of antigenemia, and the greatest expression of viral RNA and protein in the central nervous system. Macaca nemestrina were more likely to develop severe neurological lesions than M. mulatta or M. fascicularis (P = 0.048). This study demonstrated that neurovirulent strains within the virus swarm can selectively enter and become established in the central nervous system and that the neurological lesions that develop are correlated with the development of host immunosuppression. The species differences in severity of neurological lesions seen in this study suggest that host factors are also important in determining the outcome of lentiviral infection.
为了研究导致神经疾病的病毒和宿主因素，将9只猕猴静脉内共同接种SIV/DeltaB670（一种由至少21种不同基因型组成的SIV原始分离株）和SIV/17E-Fr（一种神经毒性重组克隆）。在整个感染过程中测量CD4+细胞计数和抗原血症。从脑和外周血单核细胞DNA中扩增SIV env V1区域，以比较脑和血液中存在的基因型。9只猕猴中有7只（78%）出现了典型的与SIV相关的神经病变，分为严重（4只猕猴）、中度（2只猕猴）或轻度（1只猕猴），平均安乐死时间为7个月。患有严重神经病变的猕猴进展更快，平均安乐死时间为3 - 6个月。在所有4只患有严重脑炎的猕猴的脑匀浆中检测到SIV/17E-Fr，在其中4只中的3只中，SIV/17E-Fr是在中枢神经系统中鉴定出的唯一基因型。神经病变较轻或无神经病变的猕猴脑中通常有各种基因型的SIV/DeltaB670之一。在整个感染过程中，在外周血单核细胞中检测到各种基因型的SIV/DeltaB670和SIV/17E-Fr。患有严重神经病变的猕猴CD4+细胞计数下降最为急剧，抗原血症水平最高，并且在中枢神经系统中病毒RNA和蛋白质的表达最高。豚尾猕猴比恒河猴或食蟹猕猴更有可能发生严重的神经病变（P = 0.048）。这项研究表明，病毒群体中的神经毒性菌株可以选择性地进入中枢神经系统并在其中定植，并且所发生的神经病变与宿主免疫抑制的发展相关。本研究中观察到的神经病变严重程度的物种差异表明，宿主因素在决定慢病毒感染的结果方面也很重要。
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