The role of cytomegalovirus gH/gL glycoprotein complexes in infection

巨细胞病毒gH/gL糖蛋白复合物在感染中的作用

• 批准号: 96888808
• 负责人: Privatdozentin Dr. Barbara Adler
• 金额: --
• 依托单位: Lehrstuhl für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/96888808?language=en
• 关键词: role; cytomegalovirus; gH; gL; glycoprotein

Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality in immunocompromised hosts. Though anti-HCMV therapies exist, the rapid development of resistance calls for new, complementing strategies. Common targets for antiviral therapy are for example envelope glycoproteins which promote virus entry. Herpesvirus gH/gL glycoprotein complexes are essential for fusion of the viral envelope with a cellular membrane in the process of virus entry. The core gH/gL dimer is complemented with additional proteins which can bind to specific receptors and/or may guide the virus particles through specific exit pathways. For HCMV, two alternative gH/gL complexes have been identified, which in vitro define tropism and influence virus release, yet, whose function in the human infection is not clarified. The aims of this project are to identify the cellular receptor through which HCMV gH/gL complexes define tropism for certain cell types and to identify the homologous gH/gL complexes of the murine cytomegalovirus (MCMV). Then the role of these complexes will be studied in vivo in the mouse model using deletion mutants of MCMV gH/gL complexes.

人巨细胞病毒（HCMV）感染是免疫功能低下宿主发病和死亡的主要原因。虽然存在抗HCMV疗法，但耐药性的快速发展需要新的补充策略。抗病毒治疗的常见靶标是例如促进病毒进入的包膜糖蛋白。疱疹病毒gH/gL糖蛋白复合物是病毒进入细胞过程中病毒包膜与细胞膜融合所必需的。核心gH/gL二聚体补充有额外的蛋白质，这些蛋白质可以结合特异性受体和/或可以引导病毒颗粒通过特异性出口途径。对于HCMV，已经鉴定了两种替代的gH/gL复合物，其在体外限定嗜性并影响病毒释放，然而，其在人类感染中的功能尚不清楚。该项目的目的是确定细胞受体，通过该受体HCMV gH/gL复合物确定某些细胞类型的嗜性，并确定小鼠巨细胞病毒（MCMV）的同源gH/gL复合物。然后，这些复合物的作用将在体内研究在小鼠模型中使用MCMV gH/gL复合物的缺失突变体。

项目成果

Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm

研究病毒突变体体内减毒的原则：定义巨细胞病毒 gH/gL/gO 复合物作为范例的作用

• DOI: 10.1007/s00430-015-0405-2
• 发表时间: 2015
• 期刊: Medical Microbiology and Immunology
• 影响因子: 5.4
• 作者: Podlech;Reddehase;Lemmermann
• 通讯作者: Lemmermann

Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma

• DOI: 10.1158/2326-6066.cir-14-0044
• 发表时间: 2015-05-01
• 期刊: CANCER IMMUNOLOGY RESEARCH
• 影响因子: 10.1
• 作者: Qiu, Zhijuan;Huang, Huakang;Khanna, Kamal M.
• 通讯作者: Khanna, Kamal M.