Microarray Studies to Discover Novel Host Defenses in SIV Infection

描述（由申请人提供）：预防HIV-1传播需要一种有效的疫苗。本建议旨在在siv -恒河猴动物模型中确定先前感染减毒？SIV -nef毒株。在保护程度明显不同的情况下，建议对宫颈、阴道和淋巴组织进行微阵列转录谱分析，以确定以下方面的保护相关因素：(i)先天免疫和适应性免疫的特定或新成分；（ii）先天免疫和适应性免疫反应的平衡上调，而不含促炎成分，促炎成分可招募CD4 T细胞促进局部扩张和全身感染；（iii）与先天和适应性反应的意外成分相关的保护机制，与病毒暴露的粘膜上皮反应相关的机制，或由微阵列提出的全新防御机制。这些见解可以在未来的工作中加以利用，以设计一种有效的疫苗，保护妇女免受艾滋病毒-1感染。

DESCRIPTION (provided by applicant): An effective vaccine is needed for prevention of HIV-1 transmission. This proposal is directed to identifying, in the SIV-rhesus macaque animal model, correlates of protection against vaginal transmission conferred by prior infection with an attenuated ?-nef strain of SIV. Microarray transcriptional profiling of cervical, vaginal and lymphatic tissues, at times when the extent of protection differs markedly, is proposed as a means to identify correlates of protection in: (i) particular or novel components of innate and adaptive immunity; (ii) a balanced up-regulation of innate and adaptive immune responses without the pro-inflammatory component that recruits CD4 T cells to fuel local expansion and systemic infection; and (iii) mechanisms of protection related to unexpected components of the innate and adaptive response, mechanisms related to the mucosal epithelial response to virus exposure, or wholly novel defenses suggested by the microarrays. These insights can then be harnessed in future work to design an effective vaccine to protect women from HIV-1 acquisition. PUBLIC HEALTH RELEVANCE: An effective vaccine to prevent HIV-1 is urgently needed. In this proposal, transcriptional profiles of cervical, vaginal and lymphatic tissues will be determined in infection with an attenuated ?-nef strain of SIV to identify novel correlates of protection with this vaccine approach.