Deciphering the cell type specific control of HCMV tegument-delivered pp71 subcellular localization

破译 HCMV 皮膜传递的 pp71 亚细胞定位的细胞类型特异性控制

基本信息

批准号：
10176409
负责人：
ROBERT F KALEJTA
金额：
$ 19.43万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10176409
关键词：
Acquired Immunodeficiency Syndrome Affect Antiviral Agents Attenuated Automobile Driving Brain Glioblastoma Brain Neoplasms CD34 gene Cardiovascular Diseases Cell Differentiation process Cell Nucleus Cell fusion Cells Communicable Diseases Congenital Abnormality Cytomegalovirus Cytoplasm Defect Disease Ectopic Expression Elderly Endocytosis Fibroblasts Gene Expression Genes Genetic Transcription Genome Growth Herpesviridae Heterochromatin Histones Human Immediate-Early Genes Impairment In Vitro Infection Lytic Lytic Phase Malignant Neoplasms Mediating Methods Molecular Chaperones Nuclear Ontology Organ Transplantation Pathway interactions Persons Phase Phenotype Proteins Publishing Structure Testing Time Trans-Activators Transcript Undifferentiated Viral Virion Virus Virus Diseases Work cell type experimental study fighting genetic corepressor in vitro Model knock-down latent infection overexpression transcriptome sequencing

项目摘要

Herpesviruses package virally-encoded transcriptional activating proteins into the tegument layer of their virions. The tegument transactivator encoded by human cytomegalovirus (HCMV) is the pp71 protein. When cells are productively infected, pp71 is released into the cytoplasm, translocates to the nucleus, and activates viral immediate early (IE) transcription. Herpesviruses also establish latent infections where productive phase gene expression is absent or attenuated. Tegument-delivered pp71 remains in the cytoplasm of the primary CD34+ cells where HCMV establishes latency. Thus, the subcellular localization of tegument-delivered pp71 differentially correlates with IE transcriptional activity during lytic infection (pp71 in the nucleus, IE transcription on) and latency (pp71 in the cytoplasm, IE transcription off). Here, we propose to identify the natural way in which the subcellular localization of tegument-delivered pp71 is controlled as a first step toward developing a method to artificially control it, and thus control the fate of an HCMV infection (lytic or latent).

疱疹病毒易受病毒编码的转录激活蛋白的包装到Tegument层他们的病毒体。由人类巨细胞病毒（HCMV）编码的TEGUMENT反式激活器是PP71蛋白。当细胞有效地感染细胞时，pp71被释放到细胞质中，易位到细胞核，然后立即激活病毒早期（IE）转录。疱疹病毒还建立了潜在感染没有生产期基因表达或减弱。 tegument删除的pp71仍保留在 HCMV的主要CD34+细胞的细胞质会建立潜伏期。因此， TEGUMEMENT分配的PP71在裂解感染过程中与IE转录活性差异相关（pp71 in 核，即转录）和潜伏期（pp71在细胞质中，即转录）。在这里，我们建议确定TEGUMEMENT删除PP71的亚细胞定位的自然方式被控制为开发人为控制它的方法的第一步，从而控制HCMV感染的命运（裂解或潜在）。