PATHOGENESIS OF AN X4-TROPIC VARIANT OF SIVMAC239

SIVMAC239 X4 热带变体的发病机制

• 批准号: 7958703
• 负责人: James A Hoxie
• 金额: $ 5.81万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958703
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Biopsy; Blood specimen; CCR5 gene; CD4 Positive T Lymphocytes; CXCR4 gene; Chemistry; Computer Retrieval of Information on Scientific Projects Database; Exhibits; Flow Cytometry; Funding; Grant; Health; Immune response; In Situ; In Vitro; Infection; Institution; Intestines; Leukocytes; Macaca mulatta; Measures; Monitor; Pathogenesis; Plasma; Primates; Protocols documentation; Research; Research Personnel; Resources; Source; Testing; United States National Institutes of Health; Variant; Viral; Viral Load result; Virus; Whole Blood; in vivo; lymph nodes; male; receptor

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. We have derived, in vitro, a variant of SIVmac239, termed SIVmac239-ST1, that exhibits high efficiency use of X4. We used this new virus to infect four male rhesus macaques to assess the effects of its altered co-receptor usage on in vivo viral replication and host control. In this protocol we intravenously inoculated four Rhesus macaques of Indian origin with 1X103 TCID50 of SIVmac239-ST1. Blood samples were collected for flow cytometry analysis as well as to monitor plasma viral load, humoral immune responses and the overall health of the animals (CBC and Chemistry). CSF was also collected for viral load analysis. Lymph node and intestinal biopsies were used for localization of the virus in situ as well as isolation of leukocytes and flow cytometry analysis. Physical exams were performed to monitor the overall health of the animals. All four animals became infected and had peak viral loads between 6.5 and 7.2 log copies/ml measured by bDNA. The set point of infection ranged between 3.5 and 6.5 log copies/ml. One animal became sick and was humanely euthanized 368 days post-challenge. The other three animals were humanely euthanized on 314 days (n=2) and 371 days (n=1) post-challenge. CCR5 decreased dramatically after infection in all four animals and in the lymph node of one animal. CXCR4 also decreased in the gut of two animals after infection (the other two were not tested). CD4 decreased in the gut of all four animals after infection. CD4 cells steadily declined in the whole blood of the one animal that showed signs of AIDS.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们已经在体外衍生出SIVmac 239的变体，称为SIVmac 239-ST 1，其表现出对X4的高效利用。 我们使用这种新病毒感染四只雄性恒河猴，以评估其改变的共受体使用对体内病毒复制和宿主控制的影响。在该方案中，我们用1 × 103 TCID 50的SIVmac 239-ST 1静脉内接种4只印度起源的恒河猴。 采集血样用于流式细胞术分析以及监测血浆病毒载量、体液免疫应答和动物的总体健康状况（CBC和化学）。还采集CSF用于病毒载量分析。 淋巴结和肠道活检用于病毒原位定位以及白细胞分离和流式细胞术分析。 进行体格检查以监测动物的总体健康状况。所有四只动物均被感染，通过bDNA测量的峰值病毒载量在6.5和7.2 log拷贝/ml之间。 感染的设定点范围为3.5至6.5 log拷贝/ml。一只动物生病，在攻毒后368天人道处死。 其他3只动物在攻毒后314天（n=2）和371天（n=1）人道处死。在所有四只动物和一只动物的淋巴结中，CCR 5在感染后急剧下降。 感染后，两只动物肠道中的CXCR 4也减少了（另外两只未进行测试）。 感染后，所有四只动物的肠道中的CD 4均下降。 在一只表现出艾滋病迹象的动物的全血中，CD 4细胞稳步下降。