Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing.
Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing.
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DOI：
10.1086/514053
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发表时间：
1997-08
期刊：
影响因子：
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通讯作者：
R. Shibata;Frank Maldarelli;Christine Siemon;T. Matano;Mark Parta;Georgina Miller;Torgny N. Fredrickson;Malcolm A. Martin
中科院分区：
文献类型：
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作者：
R. Shibata;Frank Maldarelli;Christine Siemon;T. Matano;Mark Parta;Georgina Miller;Torgny N. Fredrickson;Malcolm A. Martin
构建了嵌合的猴-人免疫缺陷病毒（SHIV），其携带来自T细胞-巨噬细胞双嗜性原代分离物（人免疫缺陷病毒1型[HIV-1]株DH 12）的包膜糖蛋白。当接种到猕猴，SHIV（MD 14）携带猿猴免疫缺陷病毒衍生的nef建立显着更高的病毒载量比SHIV（MD 1），其中包含HIV-1 nef基因。在受感染的猴子中观察到三种CD 4细胞耗竭模式：感染后10周内，CD 4细胞以指数方式不可逆地损失至无法检测的水平;在急性感染期间显著减少，随后部分恢复和稳定（持续10周至> 1年），在某些动物中随后下降至无法检测的水平;在急性感染期间短暂损失。诱导的免疫缺陷伴有CD 4细胞计数< 50个/μ L，并与卡氏肺孢子虫肺炎、巨细胞病毒脑膜脑炎、淋巴细胞耗竭和胸腺萎缩相关。
Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed. When inoculated into macaque monkeys, SHIV(MD14) carrying simian immunodeficiency virus-derived nef established significantly higher virus loads than did SHIV(MD1), which contains the HIV-1 nef gene. Three patterns of CD4 cell depletion were observed in infected monkeys: exponential and irreversible loss to undetectable levels within 10 weeks of infection; marked reduction during acute infection followed by partial recovery and stabilization (lasting from 10 weeks to > 1 year), with a later decline to undetectable levels in some animals; and a transient loss during acute infection. The induced immunodeficiency was accompanied by CD4 cell counts of < 50 cells/microL and was associated with Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid depletion, and thymic atrophy.