DEVELOPMENT OF INFECTIOUS CLONES OF SIVSM STRAINS BELONGING TO DIFFERENT CLADES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 与连续传代的SIVmac251/239相比，SIVsm初次分离株在Rh中的致病性明显较低。我们的假设是，使用代表不同分支的SIVsm毒株将产生更好的艾滋病发病机制模型。我们的目标是构建和鉴定SIVsm毒株的体外和体内感染性分子克隆，这些分子克隆属于不同的、明确的系统发育谱系(CLADE)。从SIV感染动物M926、M946(谱系2)、D215(谱系6)、FTQ(谱系5)和M923(谱系1，重组株)的血清中提取总RNA。这些病毒的全长测序已经完成，其他10个新的SIVsmm全长基因组已经产生。获得了SIVsmmM926的感染性克隆，目前正在进行体内外试验。剩余的克隆构建正在进行中。 一系列由免疫系统更好地控制的感染性分子克隆将为研究艾滋病免疫发病机制和研究Rh异型保护的疫苗开发提供增强和非常必要的工具。

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. Primary SIVsm isolates are significantly less pathogenic in Rh than the serially passaged SIVmac251/239. Our hypothesis is that the use of SIVsm strains representing different clades will generate a better model for AIDS pathogenesis. Our objective is to construct and characterize in vitro and in vivo infectious molecular clones of SIVsm strains belonging to different, well-defined phylogenetic lineages (clades). Total RNA from the sera of SIV infected animals M926, M946 (lineage 2), D215 (Lineage 6), FTQ (Lineage 5) and M923 (Lineage 1, recombinant strain) was isolated. Full length sequencing of these viruses is completed Other 10 new SIVsmm full length genomes has been generated. An infectious clone of SIVsmmM926 was obtained and is currently tested in vitro and in vivo. Remaining clone construction is in progress. An array of infectious molecular clones, which are better controlled by the immune system will provide enhanced and very much needed tools to the research community for AIDS immunopathogenesis and vaccine development investigating heterotypic protection in Rh.