HIV Redirecting Innate Immunity by Vpu Targeting of JAK1

HIV 通过 Vpu 靶向 JAK1 重定向先天免疫

• 批准号: 10619889
• 负责人: DAVID JESSE SANCHEZ
• 金额: $ 7.15万
• 依托单位: WESTERN UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-20 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10619889
• 关键词: Amino Acid Motifs; Biochemical; CD4 Positive T Lymphocytes; Cell physiology; Cells; Cellular Immunity; Cellular biology; Cytokine Receptors; Cytokine Signaling; Data; Dendritic Cells; Detection; Genes; Goals; HIV; HIV Infections; Immune response; Immune system; Immunity; Infection; Innate Immune Response; Innate Immune System; Interferon Type I; Interferon Type II; Interferons; JAK1 gene; Link; Lysosomes; Maps; Mediating; Methods; Mutation Analysis; Names; Natural Immunity; Outcome; Pathogenesis; Patients; Persons; Phenotype; Phosphorylation; Production; Proteins; Refractory; Research Project Grants; STAT1 gene; Serum; Signal Transduction; System; T-Lymphocyte; Techniques; Tertiary Protein Structure; Ubiquitination; Viral; Virus; Virus Diseases; Virus Replication; Work; adaptive immunity; antiviral immunity; arm; cellular targeting; cytokine; domain mapping; experience; immune clearance; insight; multicatalytic endopeptidase complex; response; tumor-immune system interactions; vpu Protein

Project Summary/Abstract It is well known that the pathogenesis of HIV is intricately linked to the immune system. For HIV to promote its replication and long-term infection HIV must also modulate cytokine signaling to manipulate the immune microenvironment HIV is existing in. In our previous work we have found that HIV has encoded accessory genes that are able to block the action of the important innate antiviral cytokine named Type I Interferon. Type I Interferons were named for their ability to interfere with the replication of viruses and HIV has encoded multiple ways to block this cytokine. The overall goal of this R03 application is to determine how one of the HIV-encoded genes that blocks Type I Interferon can block this signaling in T cells, the major cell infected by HIV. Long term, this work is critical to set the stage to better understand how HIV sustains itself in a person and avoids elimination by the innate immune system.

项目摘要/摘要 众所周知，HIV的发病机理与免疫系统复杂地联系在一起。艾滋病毒促进其 复制和长期感染HIV还必须调节细胞因子信号传导以操纵免疫 微环境艾滋病毒现有。在我们以前的工作中，我们发现艾滋病毒已编码附件 能够阻止重要的先天抗病毒细胞因子的作用的基因，称为I型干扰素。类型 我的干扰素以干扰病毒复制的能力而得名，艾滋病毒已编码 阻断这种细胞因子的多种方法。此R03应用的总体目标是确定其中之一 HIV编码的基因阻断I型干扰素可以阻止T细胞中的该信号传导，这是由感染的主要细胞 艾滋病病毒。从长远来看，这项工作对于更好地了解艾滋病毒如何维持自己的舞台至关重要 并避免先天免疫系统消除。