IMMUNOPATHOGENESIS OF CLADE C SHIV-1157IPD3N4 IN M NEMESTRINA

M Nemestrina 中 C 进化枝 SHIV-1157IPD3N4 的免疫发病机制

• 批准号: 8172757
• 负责人: Shiu-Lok Hu
• 金额: $ 46.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172757
• 关键词: Acute; Animals; CD4 Positive T Lymphocytes; Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Evolution; Family suidae; Funding; Grant; Infection; Institution; Lentivirus Infections; Macaca; Memory; Pathogenesis; Phase; Plasma; Primate Lentiviruses; Reporting; Research; Research Personnel; Resources; Simian Acquired Immunodeficiency Syndrome; Source; T-Lymphocyte; Tail; Time; Tropism; United States National Institutes of Health; Viral; Viral Genome; Viral Load result; Viremia; fitness; insight; mucosal site; neutralizing antibody; pathogen; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To gain further insight on the diversity of host-pathogen interactions and how they contribute to pathogenesis of primate lentivirus infection, we examined the sequelae of intrarectal infection with a CCR5-tropic clade C SHIV1157ipd3N4 in pigtailed macaques. We reported last year for the first time a rapid and substantial loss of CD4+ T cells at multiple mucosal sites in pigtailed macaques following SHIV infection. By 2-3 wks post-infection, profound depletion of CD4+CCR5+ T cells cells and CD28-CD95+ effector memory cells were observed, consistent with the R5-tropism of SHIV1157ipd3N4. Two of the three animals that were studied beyond the acute phase of infection showed persistent plasma viremia for 48 wks, while the remaining one controlled its plasma viral load at baseline (102 copies/ml). Cross-clade neutralizing antibodies developed in both persistently viremic animals starting at 24 weeks after infection. However, both animals developed clinical signs consistent with simian AIDS and were euthanized. We are currently studying the evolution of viral sequences in these animals to gain a better insight on changes in the viral genome that may confer greater fitness for persistent infection in pig-tailed macaques.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 为了进一步了解宿主-病原体相互作用的多样性以及它们如何促进灵长类慢病毒感染的发病机制，我们检查了猪尾猕猴中 CCR5 亲性进化枝 C SHIV1157ipd3N4 直肠内感染的后遗症。去年，我们首次报道了猪尾猕猴感染 SHIV 后多个粘膜部位 CD4+ T 细胞快速且大量损失。 感染后 2-3 周，观察到 CD4+CCR5+ T 细胞和 CD28-CD95+ 效应记忆细胞的深度消耗，与 SHIV1157ipd3N4 的 R5 向性一致。在感染急性期之后进行研究的三只动物中，有两只显示出持续 48 周的血浆病毒血症，而剩下的一只则将其血浆病毒载量控制在基线（102 拷贝/毫升）。感染后 24 周开始，两只持续病毒血症的动物均出现跨进化枝中和抗体。然而，两只动物都出现了与猿猴艾滋病一致的临床症状，并被安乐死。我们目前正在研究这些动物中病毒序列的进化，以便更好地了解病毒基因组的变化，这些变化可能使猪尾猕猴更适合持续感染。