Microarray Studies to Discover Novel Host Defenses in SIV Infection

描述（由申请人提供）：需要一种有效的疫苗来预防HIV-1传播。该建议旨在确定，在SIV-恒河猴动物模型中，与先前感染减毒？SIV nef株。当保护程度显著不同时，宫颈、阴道和淋巴组织的微阵列转录谱被提出作为鉴定以下保护相关物的手段：（i）先天性和适应性免疫的特定或新组分;（ii）先天性和适应性免疫应答的平衡上调，而没有促-炎性成分，募集CD 4 T细胞以促进局部扩张和全身感染;和（iii）与先天和适应性反应的意外成分相关的保护机制，与粘膜上皮细胞对病毒暴露的反应相关的机制，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来保护妇女免受HIV-1感染。 公共卫生相关性：迫切需要一种有效的疫苗来预防HIV-1。在这项建议中，宫颈，阴道和淋巴组织的转录谱将在感染减毒？nef株的SIV，以确定与这种疫苗方法的保护的新的相关性。

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.