Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques

Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques
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DOI:
10.1089/aid.1997.13.635
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发表时间:
1997-05-20
影响因子:
1.5
通讯作者:
Narayan, O
Narayan, O
中科院分区:
医学4区
文献类型:
--
作者:
Joag, SV;Li, ZA;Narayan, O

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通过在猕猴中进行动物间传代,我们获得了一种致病性嵌合猴-人免疫缺陷病毒(SHIV),该病毒在猪尾猕猴中引起CD 4(+)T细胞损失和AIDS,并通过阴道内和静脉内途径将其用于感染20只恒河猴和猪尾猕猴。基于感染的结果和CD 4(+)T细胞损失和病毒载量的模式,将疾病分为四种模式:急性、亚急性、慢性和非进行性感染。在研究期间,20只动物中有15只发生致命疾病,包括AIDS、脑炎、肺炎和严重贫血。在这些动物中鉴定出的寄生虫病原体包括肺孢子虫、巨细胞病毒、隐孢子虫、弓形虫和念珠菌,没有单一参数本身预测结果,尽管血液中低CD 4(+)T细胞计数、高血浆病毒水平和红细胞自身抗体的存在可靠地预测致命结果,5只动物(25%)在接种后3个月内死亡,构成急性疾病组,而9只动物(45%)患有亚急性疾病,在接种后3至8个月内死亡,这种在8个月内70%的死亡率明显短于HIV-1感染的人,其中70%在感染后10年发展为致命疾病。猕猴中的SHIV感染提供了一个有用的模型,用于评估抗病毒策略,结合了SIVmac系统的所有优点,但使用的病毒带有HIV-1的包膜基因。
By animal-to-animal passage in macaques we derived a pathogenic chimeric simian-human immunodeficiency virus (SHIV) that caused CD4(+) T cell loss and AIDS in pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the intravaginal and intravenous routes, On the basis of the outcome of infection and patterns of CD4(+) T cell loss and viral load, disease was classified into four patterns: acute, subacute, chronic, and nonprogressive infection, During the study period, 15 of the 20 animals developed fatal disease, including AIDS, encephalitis, pneumonia, and severe anemia. Opportunistic pathogens identified in these animals included Pneumocystis, cytomegalovirus, Cryptosporidium, Toxoplasma, and Candida, No single parameter by itself predicted outcome, although a combination of low CD4(+) T cell counts in blood, high plasma virus levels, and presence of autoantibodies to red blood cells reliably predicted a fatal outcome, Five animals (25%) died within 3 months of inoculation and constituted the group with acute disease, whereas the nine animals (45%) with subacute disease died between 3 and 8 months postinoculation, This 70% mortality within 8 months is significantly shorter than in HIV-1-infected human beings, of whom 70% develop fatal disease a decade after infection, SHIV infection in macaques provides a useful model with which to evaluate antiviral strategies, combining all the advantages of the SIVmac system, yet using a virus bearing the envelope gene of HIV-1.