Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus.
Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus.
复制标题
DOI：
10.1186/1742-4690-6-65
复制
发表时间：
2009-07-14
期刊：
影响因子：
3.3
通讯作者：
Hu SL
中科院分区：
文献类型：
--
作者：
Ho O;Larsen K;Polacino P;Li Y;Anderson D;Song R;Ruprecht RM;Hu SL
尽管猪尾猕猴（Macaca nemestrina）多年来一直被用于艾滋病研究，但与恒河猴（Macaca mulatta）相比，对该物种的早期免疫致病事件知之甚少。类似地，早期感染事件对于猿猴免疫缺陷病毒（SIV）有很好的特征，但对于嵌合猿-人类免疫缺陷病毒（SHIV）则较少，尽管后者已广泛用于艾滋病毒疫苗研究。在这里，我们报告了猪尾猕猴直肠内感染 CCR5 进化枝 C SHIV-1157ipd3N4 的后果。在直肠内接种 SHIV-1157ipd3N4 后，所有四只猪尾猕猴的外周血和肠道组织中均检测到血浆和细胞相关病毒。我们还观察到多个粘膜部位 CD4+ T 细胞快速且不可逆地损失，导致接种后 0.5-4 周 CD4:CD8 T 细胞比率显着下降。这种耗竭针对表达 CCR5 辅助受体并具有 CD28-CD95+ 效应记忆表型的 CD4+ T 细胞亚群，与 SHIV-1157ipd3N4 的 R5 向性一致。急性期后研究的所有三只动物早在第 4 周就发生了血清转化，其中两只动物在第 24 周时出现了跨进化枝中和抗体反应。这两只动物还表现出持续血浆病毒血症超过 48 周。其中一只动物在接种后 20 周开始出现外周血 CD4+ T 细胞耗竭，结果表明其中一只动物患上了 AIDS。这些发现表明，猪尾猕猴中 SHIV-1157ipd3N4 诱导的发病机制与感染 SIV 的恒河猴有着相似的过程。因此，猪尾猕猴的R5 SHIV-C感染可以为艾滋病疫苗和发病机制研究提供有用且相关的模型。
Although pig-tailed macaques (Macaca nemestrina) have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta). Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV), but less so for chimeric simian-human immunodeficiency viruses (SHIV), although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques. Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5–4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation. These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.
登录
查看更多内容
影响因子：
64.8
作者：
DEWHURST, S;EMBRETSON, JE;FULTZ, PN
通讯作者：
FULTZ, PN
DOI：
10.1097/01.qa1.0000017963.22053.47
发表时间：
2002-06-01
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Chen, ZW;Zhao, XQ;Ho, DD
通讯作者：
Ho, DD
DOI：
10.1073/pnas.0812587106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Hatziioannou, Theodora;Ambrose, Zandrea;Bieniasz, Paul D.
通讯作者：
Bieniasz, Paul D.
影响因子：
5.4
作者：
Chase, Amanda J.;Sedaghat, Ahmad R.;Siliciano, Robert F.
通讯作者：
Siliciano, Robert F.
影响因子：
5.4
作者：
Joag, SV;Li, Z;Narayan, O
通讯作者：
Narayan, O