MOLECULAR BASIS OF ANTIGENIC VARIATION ON MALARIA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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，不一定是研究者所在机构。本研究的基本目的是了解疟原虫变异抗原基因表达的分子机制。抗原变异是逃避宿主保护性免疫应答的基本适应，并且是促成慢性血液感染建立的主要因素之一。经典的诺氏疟原虫-恒河猴疟疾模型是研究的主要焦点。这种猿疟疾模型适合于体外和体内研究，并且在诱导的顺序转换后表达不同SICA（裂殖体感染细胞凝集）变体抗原表型的诺氏疟原虫H株的独特稳定克隆可以在幼稚恒河猴中多次体内传代（60代）后保持。这些同基因克隆系为研究克隆抗原变异的细胞和遗传机制提供了一个特殊的工具。最近，我们还开始了对疟疾变异抗原的补充研究，使用猴疟疾，P. coatneyi，因为该物种具有类似的周期性，形态学和免疫病理生理学特征，可与最严重的人类疟疾，P. falciparum相比。过去一年的研究集中在SICAvar基因家族的持续全基因组分析和开发与我们的转录后基因沉默作为控制变体抗原基因表达的机制的假说相关的分子数据的研究。

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 basic objective of this research is to understand the molecular mechanisms that govern variant antigen gene expression in Plasmodium. Antigenic variation is a fundamental adaptation to evade a host protective immune response and is one of the major factors contributing to the establishment of chronic blood infections. The classic P. knowlesi-rhesus monkey model of malaria is the primary focus of investigations. This simian malaria model is amenable to both in vitro and in vivo studies and unique stable clones of the P. knowlesi H strain expressing distinct SICA (Schizont Infected Cell Agglutination) variant antigen phenotypes after induced sequential switchings can be maintained after numerous in vivo passages (60 generations) in naive rhesus monkeys. These isogenic clonal lines provide a special tool for studies of the cellular and genetic mechanisms underlying clonal antigenic variation. Recently, we have also initiated complementary investigations on malaria variant antigens using the simian malaria, P. coatneyi, since this species has a similar periodicity, and morphological and immunopathophysiological characteristics that are comparable to the most severe human malaria, P. falciparum. Studies this past year have focused on continued genome wide analyses of the SICAvar gene family and studies developing molecular data relating to our hypothesis of post transcriptional gene silencing as a mechanism to control variant antigen gene expression.