Abstract:
Nonhuman primate (NHP) biomedical models are critical to our understanding of human health and disease, yet we are still in the early stages of developing sufficient tools to support primate genomic research that allow us to better understand the basis of phenotypic traits in NHP models of disease. A mere 7 years ago, the limited NHP transcriptome profiling that was being performed was done using complementary DNA arrays based on human genome sequences, and the lack of NHP genomic information and immunologic reagents precluded the use of NHPs in functional genomic studies. Since then, significant strides have been made in developing genomics capabilities for NHP research, from the rhesus macaque genome sequencing project to the construction of the first macaque-specific high-density oligonucleotide microarray, paving the way for further resource development and additional primate sequencing projects. Complete published draft genome sequences are now available for the chimpanzee ( Chimpanzee Sequencing Analysis Consortium 2005), bonobo ( Prufer et al. 2012), gorilla ( Scally et al. 2012), and baboon ( Ensembl.org 2013), along with the recently completed draft genomes for the cynomolgus macaque and Chinese rhesus macaque. Against this backdrop of both expanding sequence data and the early application of sequence-derived DNA microarrays tools, we will contextualize the development of these community resources and their application to infectious disease research through a literature review of NHP models of acquired immune deficiency syndrome and models of respiratory virus infection. In particular, we will review the use of -omics approaches in studies of simian immunodeficiency virus and respiratory virus pathogenesis and vaccine development, emphasizing the acute and innate responses and the relationship of these to the course of disease and to the evolution of adaptive immunity.
摘要:
非人灵长类动物(NHP)的生物医学模型对于我们理解人类健康和疾病至关重要。然而,我们仍处于开发足够工具来支持灵长类动物基因组研究的早期阶段,这些工具使我们能够更好地了解NHP疾病模型中表型性状的基础.仅仅7年前,正在进行的有限的NHP转录组分析是使用基于人类基因组序列的互补DNA阵列完成的,NHP基因组信息和免疫试剂的缺乏阻碍了NHP在功能基因组研究中的应用。从那以后,在开发用于NHP研究的基因组学能力方面取得了重大进展,从恒河猴基因组测序项目到第一个猕猴特异性高密度寡核苷酸微阵列的构建,为进一步的资源开发和其他灵长类动物测序项目铺平道路。现在已为黑猩猩提供完整的基因组序列草案(黑猩猩测序分析协会,2005年),黑猩猩(Prufer等人。2012),大猩猩(Scally等人。2012),和狒狒(Ensembl.org2013),以及最近完成的食蟹猴和中国恒河猴基因组草案。在扩展序列数据和序列来源的DNA微阵列工具的早期应用的背景下,我们将通过对获得性免疫缺陷综合征NHP模型和呼吸道病毒感染模型的文献综述,了解这些社区资源的开发及其在传染病研究中的应用.特别是,我们将回顾-组学方法在猿猴免疫缺陷病毒和呼吸道病毒发病机理和疫苗开发研究中的应用,强调急性和先天反应以及这些反应与疾病进程和适应性免疫进化的关系。