A novel cytosolic chaperone complex in polyomavirus ER membrane transport

多瘤病毒内质网膜转运中的新型胞质伴侣复合物

• 批准号: 8850542
• 负责人: Billy Tsai
• 金额: $ 29.86万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8850542
• 关键词: BK Virus; Binding; Biochemical; Cell Nucleus; Cell membrane; Cells; Complex; Crude Extracts; Cystitis; Cytosol; DNA Tumor Viruses; Data; Endocytosis; Endoplasmic Reticulum; Event; Family; Genetic Transcription; Guanine Nucleotide Exchange Factors; Human; Human poliovirus; Infection; JC Virus; Kidney Diseases; Laboratory Study; Lead; Lytic Phase; Malignant Neoplasms; Membrane; Merkel Cells; Molecular; Molecular Chaperones; Molecular Target; Nucleic Acids; Nucleotides; Papillomavirus; Pathway interactions; Penetration; Phase; Physiological; Polioviruses; Polyomavirus; Polyomavirus Infections; Process; Progressive Multifocal Leukoencephalopathy; Proteins; Role; Skin Cancer; Therapeutic Intervention; Transmembrane Transport; Viral; Viral Genome; Virus; base; glycolipid receptor; human disease; insight; metaplastic cell transformation; nervous system disorder; novel; particle; prevent; public health relevance; therapeutic development; trafficking

 DESCRIPTION (provided by applicant): The objective of this application is to clarify how a novel cytosolic chaperone complex promotes endoplasmic reticulum (ER) membrane penetration of the non-enveloped virus polyomavirus (Py). To cause infection, Py engages a host glycolipid receptor on the plasma membrane, becomes endocytosed, and traffics to the ER lumen. Here the viral particle undergoes conformational changes to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus where transcription and replication of the viral genome ensue, leading to lytic infection or cellular transformation. How Py enters the cytosol from the ER is a crucial yet poorly understood event. Particularly enigmatic are cytosolic events that regulate this ER membrane penetration process. Accordingly this application is focused on elucidating the role of the so-called BHS cytosolic chaperone complex in ejecting Py into the cytosol from the ER.