Membrane Traffic Pathways in Viral Replication and Pathogenesis

病毒复制和发病机制中的膜运输途径

• 批准号: MC_UU_00012/1
• 负责人: Mark Marsh
• 金额: $ 137.49万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00012%2F1
• 关键词: Membrane; Traffic; Pathways; Viral; Replication

Whether direct infections of man or infections that impact on domestic animals, crops or the environment in general, virus infections are a major health and economic burdens for mankind. Viruses require cells for infection and replication. Understanding the various ways in which viruses gain entry to cells, exploit cellular mechanisms for their replication and exert their pathogenic potential is key to intervening in these processes. Our work aims to understand aspects of the cell biology of human immunodeficiency viruses (HIV), the infectious agents associated with AIDS, and the arboviruses Dengue virus and Semliki Forest virus, representatives of two families of viruses transmitted by mosquitoes and currently responsible for wide-spread epidemics in the tropics. We will focus on understanding how a set of cellular proteins can prevent specific events in the entry of these viruses into cells, with a view to exploiting these proteins as natural inhibitors of infection. In parallel, we aim to use knowledge acquired over many years to identify broad-spectrum, small molecule, inhibitors of arbovirus infection that can be used as prophylactics or in epidemic situations. We will continue current work on virus assembly, using new methods to understand the cell biology of virus formation and, for HIV in particular, how modification of key signals in viral proteins, required for correct virus assembly, impact on viral pathogenesis.

无论是人类的直接感染还是影响家畜、作物或一般环境的感染，病毒感染都是人类的主要健康和经济负担。病毒需要细胞进行感染和复制。了解病毒进入细胞、利用细胞机制进行复制和发挥其致病潜力的各种方式是干预这些过程的关键。我们的工作旨在了解人类免疫缺陷病毒（HIV）的细胞生物学方面，与艾滋病有关的传染性病原体，以及虫媒病毒登革热病毒和塞姆利基森林病毒，这两种病毒由蚊子传播，目前在热带地区广泛传播。我们将专注于了解一组细胞蛋白质如何阻止这些病毒进入细胞的特定事件，以期利用这些蛋白质作为感染的天然抑制剂。与此同时，我们的目标是利用多年来获得的知识，以确定广谱，小分子，虫媒病毒感染的抑制剂，可用作药物或在流行病的情况。我们将继续目前在病毒组装方面的工作，使用新的方法来了解病毒形成的细胞生物学，特别是对于HIV，如何修改病毒蛋白中的关键信号，这些信号是正确的病毒组装所必需的，影响病毒的发病机制。

项目成果

A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection.

• DOI: 10.1371/journal.ppat.1010507
• 发表时间: 2022-06
• 期刊: PLoS pathogens
• 影响因子: 6.7

Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes.

• DOI: 10.1371/journal.ppat.1006835
• 发表时间: 2018-01
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Mazzon M;Castro C;Thaa B;Liu L;Mutso M;Liu X;Mahalingam S;Griffin JL;Marsh M;McInerney GM
• 通讯作者: McInerney GM

The Nef protein of the macrophage tropic HIV-1 strain AD8 counteracts human Bst-2/tetherin

巨噬细胞嗜性 HIV-1 病毒株 AD8 的 Nef 蛋白对抗人类 Bst-2/tetherin

• DOI: 10.1101/2020.02.07.938464
• 发表时间: 2020
• 作者: Giese S

Correction: Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain.

更正：Bat IFITM3 限制取决于 S-棕榈酰化和 CD225 结构域内的多态性位点。

• DOI: 10.26508/lsa.202000747
• 发表时间: 2020
• 期刊: Life science alliance
• 影响因子: 4.4
• 作者: Benfield CT