A DECLINE IN CC-CHEMOKINE GENE EXPRESSION DURING PRIMARY SHIV INFECTION

原发性 SHIV 感染期间 CC 趋化因子基因表达下降

• 批准号: 7562335
• 负责人: KAROL SESTAK
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562335
• 关键词: CCL3 gene; CCL4 gene; CCL5 gene; CD4 Positive T Lymphocytes; Cell Count; Cells; Chronic; Colon; Computer Retrieval of Information on Scientific Projects Database; Confocal Microscopy; Flow Cytometry; Funding; Gene Expression; Genus Cola; Grant; Gut associated lymphoid tissue; HIV; In Vitro; Infection; Institution; Macaca mulatta; Measures; Mesentery; Messenger RNA; Modeling; Plasma; Polymerase Chain Reaction; Production; RANTES; Research; Research Personnel; Resources; Source; Staging; Testing; Time; United States National Institutes of Health; Viral; Viral Load result; Viremia; Virus; Virus Diseases; beta-Chemokines; day; jejunum; lymph nodes; peripheral blood; response; 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. The CC-chemokines CCL3, CCL4 and CCL5 have been found to block the entry of CCR5-tropic HIV into host cells and to suppress the viral replication in vitro. Main objective of this study was to evaluate the host CCL3, CCL4 and CCL5 gene expression in response to simian-human immunodeficiency virus (SHIV) infection in rhesus macaque model. Five rhesus macaques were inoculated with CCR5-tropic SHIVSF162P4. The mRNA levels of CCL3, CCL4 and CCL5 were measured by real-time PCR at post inoculation day (PID) 0, 7, 14, 21, 35, 56 and 180 in peripheral blood. In addition, gut-associated lymphoid tissues (GALT) e.g. jejunum, colon and mesenteric lymph nodes (MLN) collected at PID 0, 14 and 180 were tested. Plasma viral loads and peripheral blood CD4+ T cell counts were used as indicators of the viral infection. A decline in CC-chemokine gene expression was found during primary (PID 7-21), but not during chronic (PID 180) stage of infection. The lowest gene expression levels at PID 14 coincided with the peak of viremia. Compared with PID 0, expressions of all three CC-chemokines were decreased (p0.05) at PID14 in peripheral blood. Moreover, CCL3 and CCL4 were decreased (p0.05) at PID 14 in all three GALTs. Gene expression results were corroborated by flow cytometry and confocal microscopy. Decline of CC-chemokine production during primary SHIV infection may thus facilitate further spread of the virus.

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。 CC趋化因子CCL 3、CCL 4和CCL 5在体外可阻断嗜CCR 5的HIV进入宿主细胞并抑制病毒复制。本研究的主要目的是评估宿主CCL 3、CCL 4和CCL 5基因在猴-人免疫缺陷病毒（SHIV）感染恒河猴模型中的表达。用CCR 5-嗜性SHIVSF 162 P4接种5只恒河猴。在接种后第0、7、14、21、35、56和180天（PID），通过实时荧光PCR测定外周血中CCL 3、CCL 4和CCL 5的mRNA水平。此外，检测了在PID 0、14和180采集的肠道相关淋巴组织（GALT），例如空肠、结肠和肠系膜淋巴结（MLN）。血浆病毒载量和外周血CD 4 + T细胞计数用作病毒感染的指标。CC-趋化因子基因表达的下降被发现在原发性（PID 7-21），但不是在慢性（PID 180）感染阶段。PID 14时的最低基因表达水平与病毒血症的峰值一致。与PID 0相比，PID 14时外周血中所有三种CC-趋化因子的表达均降低（p0.05）。此外，在PID 14时，所有3种GALT中的CCL 3和CCL 4均降低（p 0.05）。基因表达结果通过流式细胞术和共聚焦显微镜证实。因此，在原发性SHIV感染期间CC-趋化因子产生的下降可能促进病毒的进一步传播。