CELL SURFACE PROTEINS INVOLVED IN ECHOVIRUS ATTACHMENT

参与艾柯病毒附着的细胞表面蛋白

• 批准号: 2667722
• 负责人: Robert William Finberg
• 金额: $ 30.32万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2667722
• 关键词: Enterovirus; binding proteins; complement; cytolysis; decay accelerating factor; fluorescence microscopy; genetic mapping; laboratory mouse; membrane proteins; molecular site; monoclonal antibody; phosphatidylinositols; protein sequence; protein structure function; receptor binding; receptor expression; tissue /cell culture; virus classification; virus infection mechanism; virus receptors; virus replication

Echoviruses are human picornaviruses which are responsible for a number of clinical syndromes including fatal disseminated infections in neonates and immunocompromised hosts as well as fever, and skin rashes in normal hosts. As a group the 32 serotypes of echovirus are the major cause of meningitis in the United States. Virus receptors are cell surface proteins which allow for virus binding to the host cell, the initial step in viral replication in mammalian cells. These proteins are often directly responsible for the tropism of the virus, and transfection of viral receptor cDNA can confer susceptibility upon cells which were not previously susceptible to infection. We have previously defined VLA/2 (an alpha2 beta1 integrin) as the receptor for echoviruses 1 and 8. Utilizing mouse-human chimeric proteins we have been able to map the echovirus binding site on VLA/2. Our recent data indicates that the I region of the alpha chain of VLA/2 is capable of binding echovirus and conferring susceptibility to infection to non- permissive cells. In this proposal we plan to map the binding site for echovirus type 1 at the amino acid level and prepare isolated I region protein to allow a detailed study of the virus host interaction with the long term goal of crystallizing both the virus and host receptor molecules. In addition we have now found that the glycosyl phosphatidyl inositol (GPI) linked complement regulatory protein Decay Accelerating Factor (DAF) is the receptor for a number of other echoviruses. This protein, which is composed of 4 short consensus repeat sequences attached to a GPI tail is highly expressed on the surface of endothelial cells and epithelial cells. It exists in a variety of soluble and membrane anchored forms in humans. We plan to define the DAF binding sites and investigate the role that this protein has in viral tropism and infectivity. Using DAF transfectants we will assess the role of the GPI tail in viral entry and replication. Finally our data indicate that several other echoviruses bind to an as yet undefined protein(s). Therefore we plan to finish our grouping of the echoviruses by defining the receptors for the remaining viruses to begin to understand echovirus tropism and pathogenesis.

埃可病毒是一种人类小核糖核酸病毒，它造成了许多