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

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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，但内源性CC趋化因子在体内HIV-1感染中的作用尚不完全清楚。在本研究中，灵长类宿主CCL 3，CCL 4和CCL 5基因表达的猴-人免疫缺陷病毒（SHIV）感染的恒河猴模型进行了评估。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，包括来自CXCR 4-嗜性SHIVKu 1感染的猕猴的选定样本子集，目的是比较由两种SHIV引起的CC-趋化因子下调的差异。还通过流式细胞术和共聚焦显微镜检测了从SHIVSF 162 P4感染的动物收集的肠道相关淋巴组织（GALT），以证实基因表达结果。可以预见的是，在PID 14时，在感染SHIVKu 1的猕猴中观察到比感染SHIVSF 162 P4的猕猴更高的病毒载量和CD 4 + T细胞损失。CC-趋化因子基因表达的下降也被发现在原发性（PID 7-21），但不是慢性（PID 180）感染阶段。确定A）SHIVSF 162 P4在感染的急性期下调CC-趋化因子基因表达的程度大于SHIVKu 1（p0.05），并且B）这种下调不与CD 4 + T细胞耗竭相关联。CC-趋化因子增强免疫调节剂，如合成的CpG-寡核苷酸的评价可以在未来的HIV疫苗研究中探索。

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, but the in vivo role of endogenous CC-chemokines in HIV-1 infection is still incompletely understood. In this study, the primate host CCL3, CCL4 and CCL5 gene expression was evaluated 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, a selected subset of samples from CXCR4-tropic SHIVKu1-infected macaques was included with objective to compare the differences in CC-chemokine down-regulation caused by the two SHIVs. Gut-associated lymphoid tissues (GALT) collected from SHIVSF162P4-infected animals were also tested by flow cytometry and confocal microscopy to corroborate the gene expression results. Predictably, higher viral loads and CD4+ T cell losses were observed at PID 14 in macaques infected with SHIVKu1 than with SHIVSF162P4. A decline in CC-chemokine gene expression was also found during primary (PID 7-21), but not chronic (PID 180) stage of infection. It was determined that A) SHIVSF162P4 down-regulated the CC-chemokine gene expression during acute stage of infection to a greater extent (p0.05) than SHIVKu1, and B) such down-regulation was not paralleled with the CD4+ T cell depletion. Evaluation of CC-chemokine enhancing immunomodulators such as synthetic CpG-oligonucleotides could be explored in future HIV vaccine studies.