Role of Cellular Sialidase in Pathogenesis of HIV-1

描述（由申请人提供）：近期和长期职业目标：（i） 在大型医疗中心进行临床相关研究，（ii） 护理传染病/内科病房的病人，以及（iii）培训 研究生、医学研究员和住院医生。 研究职业发展计划：我现在处于职业生涯的一个阶段， 临床技能扎实，需要培训才能发展扎实的研究 程序.培训期间的一个主要目标是获得 科学和组织方面的专门知识， 独立开展创新生物医学研究。我将通过以下方式实现这一目标： 增加我对糖生物学，病毒细胞相互作用和新的 分子和细胞生物学技术， 来评估我的数据研究，学术 人类病毒学和医学研究所的临床环境 中心的马里兰州大学将提供完美的机会， 实现这些目标。 研究-背景和目的：糖蛋白的生物活性 分布在自然界中的唾液酸的调节 内容神经氨酸酶（在哺乳动物细胞中称为唾液酸酶） 糖缀合物的末端唾液酸残基，从而影响蛋白质和 细胞功能我们已经证明， PBMC的表面增强HIV-1的感染性。本提案的目的是 （1）阐明细胞脱唾液酸化与细胞凋亡之间的关系。 通过确定（1）糖蛋白与PBMC被HIV-1感染之间的关系， 纯化的淋巴细胞和单核细胞的去唾液酸化促进感染和（2） 糖苷的量和类型之间存在直接的相关性， 从细胞表面去除的唾液酸的连接和 增强感染性和（II）阐明的机制（S）为 通过确定是否（1）增强HIV-1在去唾液酸化PBMC中的生长 细胞表面糖缀合物的去唾液酸化影响细胞内的早期事件， 病毒-细胞相互作用，（2）CD 4和HIV-1的辅助受体， 在活化的PBMC中相对低唾液酸化和（3）细胞的去唾液酸化 表面糖缀合物活化PBMC，诱导细胞因子的产生，或 上调CD 4和HIV-1共受体的表面表达。

DESCRIPTION (provided by applicant): Immediate and long-term career goals: (i) To conduct clinically-relevant research at a major medical center, (ii) To care for patients on an Infectious Diseases/Medicine ward and (iii) To train graduate students and medical fellows and residents. Research career development plan: I am now at a point in my career where my clinical skills are solid and need the training to develop a solid research program. A major objective during this training period is to acquire the scientific and organizational expertise needed to conduct competitive and innovative biomedical research independently. I will achieve this goal by increasing my knowledge of glycobiology, virus-cell interactions and new techniques of molecular and cellular biology and by developing an appreciation of statistical analyses with which to evaluate my data. The research, academic and clinical environments of the Institute of Human Virology and the Medical Center of the University of Maryland will provide the perfect opportunities to meet these goals. Research - Background and Aims: The biological activity of glycoproteins distributed throughout nature is influenced by modulation of their sialic acid content. Neuraminidase (referred to as sialidase in mammalian cells) removes terminal sialyl residues from glycoconjugates, and thus influences protein and cell function. We have demonstrated that desialylation of glycoconjugates on the surface of PBMCs enhances infectivity of HIV-1. The aims of this proposal are (I) to clarify the relationship between desialylation of cellular glycoproteins and infection of PBMCs by HIV-l by determining whether (1) desialylation of purified lymphocytes and monocytes promotes infection and (2) there is a direct correlation between the amount and type of glycosidic linkage of sialic acid removed from the cell surface and the degree of enhancement in infectivity and (II) to elucidate the mechanism(s) for the enhanced growth of HIV -1 in desialylated PBMCs by determining whether (1) desialylation of cellular surface glycoconjugates influences early events in the virus-cell interaction, (2) CD4 and the co-receptors for HIV-1 are relatively hyposialylated in activated PBMCs and (3) desialylation of cellular surface glycoconjugates activates PBMCs, induces production of cytokines or upregulates the surface expression of CD4 and co-receptors for HIV-1.