Generation of the Pathogenic R5-Tropic Simian/Human Immunodeficiency Virus SHIVAD8 by Serial Passaging in Rhesus Macaques
Generation of the Pathogenic R5-Tropic Simian/Human Immunodeficiency Virus SHIVAD8 by Serial Passaging in Rhesus Macaques
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DOI：
10.1128/jvi.02279-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Martin, Malcolm A.
中科院分区：
文献类型：
--
作者：
Nishimura, Yoshiaki;Shingai, Masashi;Martin, Malcolm A.
一种新的致病性R5嗜性猴/人免疫缺陷病毒（SHIV）在恒河猴中连续传代后产生。接种SHIVAD 8传代谱系的所有13只动物均经历了CD 4（+）T细胞的显著耗竭。这些感染猴中有10只成为正常进展者（NP），记忆和初始CD 4（+）T淋巴细胞逐渐丧失，产生抗病毒CD 4（+）和CD 8（+）T细胞应答，并持续慢性免疫激活，同时维持可变水平的血浆病毒血症（感染后3年内10（2）至10（5）RNA拷贝/ml）。迄今为止，5名NP发展出与卡氏肺孢子虫、鸟分枝杆菌和结肠弯曲杆菌引起的机会性感染相关的AIDS，需要在感染后100至199周之间实施安乐死。其他三种NP在感染1至2年后经历了循环CD 4（+）T淋巴细胞（92至154个细胞/μ l）的显著消耗。当测试辅助受体使用时，在安乐死时从四个NP分离的病毒保持R5嗜性。在13只接种SHIVAD 8的猕猴中，有3只出现了快速进展综合征，其特征是持续的血浆病毒血症>1 x 107 RNA拷贝/ml，记忆性CD 4（+）T细胞迅速不可逆地丧失，需要在感染后19至23周之间实施安乐死。持续的病毒血症、相关的CD 4（+）T淋巴细胞的耗竭和AIDS的诱导使得SHIVAD 8病毒谱系成为疫苗研究的潜在有价值的试剂。
A new pathogenic R5-tropic simian/human immunodeficiency virus (SHIV) was generated following serial passaging in rhesus macaques. All 13 animals inoculated with SHIVAD8 passaged lineages experienced marked depletions of CD4(+) T cells. Ten of these infected monkeys became normal progressors (NPs) and had gradual losses of both memory and naive CD4(+) T lymphocytes, generated antiviral CD4(+) and CD8(+) T cell responses, and sustained chronic immune activation while maintaining variable levels of plasma viremia (10(2) to 10(5) RNA copies/ml for up to 3 years postinfection [p.i.]). To date, five NPs developed AIDS associated with opportunistic infections caused by Pneumocystis carinii, Mycobacterium avium, and Campylobacter coli that required euthanasia between weeks 100 and 199 p.i. Three other NPs have experienced marked depletions of circulating CD4(+) T lymphocytes (92 to 154 cells/mu l) following 1 to 2 years of infection. When tested for coreceptor usage, the viruses isolated from four NPs at the time of their euthanasia remained R5 tropic. Three of the 13 SHIVAD8-inoculated macaques experienced a rapid-progressor syndrome characterized by sustained plasma viremia of >1 x 107 RNA copies/ml and rapid irreversible loss of memory CD4(+) T cells that required euthanasia between weeks 19 and 23 postinfection. The sustained viremia, associated depletion of CD4(+) T lymphocytes, and induction of AIDS make the SHIVAD8 lineage of viruses a potentially valuable reagent for vaccine studies.