Carballal G, Oubiña J R, Molinas F C, Nagle C, de la Vega M T, Videla C, Elsner B
J Med Virol. 1987 Mar;21(3):257-68. doi: 10.1002/jmv.1890210309.
To assess the usefulness of the South American primate Cebus apella as a model for neurovirulence of Junín virus, eight monkeys were inoculated with 10(5) LD50 of the attenuated XJ-Clone 3 Junín virus strain by the intrathalamic route. After the second week, weight loss and polyadenopathies were observed in most animals, one-half of which had a transient leukothrombocytopenia. Moderate clinical central nervous system (CNS) involvement was present in four of eight monkeys, while the rest had only mild neurologic signs. All recovered except one, which developed a deep coma and was killed in a pre-mortem stage at 18 days post-infection (pi). Junín virus was isolated from the throat from five, from the blood from three, and from the brain from two monkeys. In the most severely ill animal, virus titers higher than viremia were detected in both inoculated and contralateral brain hemispheres, as well as in lung, lymph node, and small intestine. Junín antigens and "in vivo" bound immunoglobulins were detected by immunofluorescence (IF) in the brain of four animals at 18, 21, 40, and 155 days pi. Moderate lymphocytic parenchymal and meningeal infiltration were observed in the brain of four animals, and gliosis was also present in the most affected monkey. Although the clinical response to infection was not uniform, all infected monkeys developed high IF antibodies. Cebus apella cannot be used as a highly sensitive model for Argentine hemorrhagic fever (AHF). However, the results obtained show that the XJ-Clone 3 strain can replicate in the primate CNS and to induce lesions and immunoglobulin deposition. In addition, viral persistence is suggested by the late detection of viral antigens in brain at 40 and 155 days pi.
为评估南美灵长类动物白喉卷尾猴作为胡宁病毒神经毒力模型的实用性,通过丘脑内途径给8只猴子接种了10(5) LD50的减毒XJ - Clone 3胡宁病毒株。第二周后,大多数动物出现体重减轻和多处淋巴结病,其中一半动物有短暂的白细胞血小板减少症。8只猴子中有4只出现中度临床中枢神经系统(CNS)受累,其余猴子只有轻微的神经体征。除1只猴子外,所有猴子均康复,这只猴子在感染后18天(pi)进入深度昏迷并在死前阶段死亡。从5只猴子的咽喉、3只猴子的血液和2只猴子的大脑中分离出胡宁病毒。在病情最严重的动物中,在接种侧和对侧脑半球以及肺、淋巴结和小肠中检测到的病毒滴度高于病毒血症。在感染后18、21、40和155天,通过免疫荧光(IF)在4只动物的大脑中检测到胡宁抗原和“体内”结合的免疫球蛋白。在4只动物的大脑中观察到中度淋巴细胞实质和脑膜浸润,在受影响最严重的猴子中也存在胶质增生。尽管对感染的临床反应并不一致,但所有感染的猴子都产生了高IF抗体。白喉卷尾猴不能用作阿根廷出血热(AHF)的高敏感性模型。然而,所获得的结果表明,XJ - Clone 3株可在灵长类动物中枢神经系统中复制并诱导病变和免疫球蛋白沉积。此外,在感染后40天和155天在大脑中晚期检测到病毒抗原提示病毒持续存在。