Immune Evasion Mechanisms of Ectromelia Virus

湿疣病毒的免疫逃避机制

• 批准号: 7641548
• 负责人: Daved H. Fremont
• 金额: $ 39.35万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7641548
• 关键词: Address; Antiviral Response; Baculoviruses; Binding; Biochemical; Bioinformatics; Biological Assay; Biological Models; C Type Lectin Receptors; CD30L; Cell Separation; Cell membrane; Cells; Collaborations; Complex; Coupled; Crystallography; DNA Viruses; Diamond; Disease; Double Stranded DNA Virus; Family; Generations; Genes; Genome; Glycoproteins; Human; Immune; Immune response; Immune system; In Vitro; Infectious Ectromelia; Insecta; Interferon Type II; Interferon-alpha; Interleukin-11; Interleukin-18; Investigation; Kinetics; Ligands; Literature; Mediating; Membrane Proteins; Moscow; Mouse Pox Virus; Mus; Mutagenesis; Open Reading Frames; Orthopoxvirus; Population; Poxviridae; Production; Proteins; Reagent; Research; Review Literature; Rodent; Role; Smallpox; Smallpox Viruses; Staining method; Stains; Structure; System; Testing; Thermodynamics; Variant; Viral; Viral Proteins; Virulent; Virus; Virus Diseases; West Nile virus; Work; base; beta-Chemokines; chemokine; cytokine; design; immunoregulation; in vivo; man; member; mouse model; pathogen; protein function; protein structure; receptor; research study; size; structural genomics; tool

Poxviruses are a family of large DNA viruses that encode up to 200 distinct open reading frames. The large size of the poxvirus genome is an important feature that has allowed them to acquire multiple immunomodulatory genes and thereby evolve unique strategies for evasion from host antiviral responses. Ectromelia virus (EV) is a member of the orthopoxvirus family and is a highly virulent rodent pathogen that causes the disease mousepox. EV is similar to variola virus, the causative agent of human smallpox. Our primary hypothesis is that secreted and cell membrane associated proteins encoded by EV likely serve important roles in viral evasion of host mediated innate and adaptive immune responses. Using a bioinformatics approach coupled to the established literature, we have selected 28 target proteins from the EV Moscow strain genome that will be investigated by a combination of biochemical, functional, and crystallographic tools in a highthroughput, structural genomics style approach. Our primary targets of investigation include the seven known cytokine and chemokine decoy receptors encoded by the virus that are specific for TNE CD30L, IL-18, IFN-alpha, IFN-gamma, IL-lbeta, and CC-chemokines. We are also targeting three proteins with sequence similarity to natural killer receptors of the C-type lectin family. We have the following specific aims for the exploration of these potential agents of immune subterfuge: (1) Establish baculovirus and bacterial oxidative refolding expression systems for targeted EV encoded proteins to be used in functional and structural studies; (2) Identify and characterize the interactions between EV proteins and their host ligands and receptors; (3) Determine the structural basis of EV protein function by x-ray crystallography and structure-based mutagenesis.

痘病毒是一种大型DNA病毒家族，可编码多达200种不同的开放阅读框。