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_12018/1
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_12018%2F1
• 关键词: Membrane; traffic; pathways; viral; replication

"We study the human immunodeficiency virus (HIV) that is linked to AIDS and is believed to have infected 60 million people worldwide. During infection these viruses must interact with receptor proteins expressed on the surfaces of target cells. Using the natural binding proteins of these receptors, it is possible to abrogate HIV infection. We are trying to understand the cellular and molecular mechanisms that underlie this regulation with the aim of developing novel strategies to down regulate the receptors. Such strategies may have efficacy against HIV. Importantly, the receptors exploited by HIV are representative of a large class of similar proteins, so-called G protein coupled receptors (GPCRs), that control a range of biological functions including the immune system. So what we learn about HIV receptors may have relevance to other important biological events.||In addition to understanding virus entry, we also investigate the molecular and cellular mechanisms involved in the formation of new virus particles within infected cells. This requires that the key structural proteins that make up virus particles are bought together at the same time and place within an infected cell so that virus particles can form. We have identified molecular signals in the envelope glycoprotein that are required for the correct trafficking within infected cells. When one of these signals is mutated in a simian model system, the virus is attenuated and is no longer pathogenic. Moreover, animals treated with this virus are protected against challenge with normal pathogenic viruses. Together these studies are providing novel insights to the mechanisms of pathogenesis and may give hints to the key components of immune control."

我们研究人类免疫缺陷病毒(HIV)，这种病毒与艾滋病有关，据信已经感染了全球6000万人。在感染过程中，这些病毒必须与目标细胞表面表达的受体蛋白相互作用。使用这些受体的天然结合蛋白，有可能根除艾滋病毒感染。我们正试图了解这种调控背后的细胞和分子机制，目的是开发新的策略来下调受体。这样的策略可能对艾滋病毒有效。重要的是，HIV利用的受体代表了一大类类似的蛋白质，即所谓的G蛋白偶联受体(GPCRs)，它们控制着包括免疫系统在内的一系列生物功能。因此，我们对HIV受体的了解可能与其他重要的生物事件相关。||除了了解病毒进入，我们还研究了在感染细胞内形成新病毒颗粒所涉及的分子和细胞机制。这需要将构成病毒颗粒的关键结构蛋白同时购买，并放置在受感染的细胞内，这样才能形成病毒颗粒。我们已经确定了包膜糖蛋白中的分子信号，这些信号是在感染细胞内正确运输所必需的。当这些信号中的一个在猿类模型系统中发生突变时，病毒就会减弱，不再具有致病性。此外，用这种病毒治疗的动物可以免受正常致病病毒的攻击。总而言之，这些研究为发病机制提供了新的见解，并可能为免疫控制的关键组成部分提供线索。

项目成果

Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis.

• DOI: 10.1038/ncomms12111
• 发表时间: 2016-07-20
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Banushi B;Forneris F;Straatman-Iwanowska A;Strange A;Lyne AM;Rogerson C;Burden JJ;Heywood WE;Hanley J;Doykov I;Straatman KR;Smith H;Bem D;Kriston-Vizi J;Ariceta G;Risteli M;Wang C;Ardill RE;Zaniew M;Latka-Grot J;Waddington SN;Howe SJ;Ferraro F;Gjinovci A;Lawrence S;Marsh M;Girolami M;Bozec L;Mills K;Gissen P
• 通讯作者: Gissen P

Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.

• DOI: 10.1371/journal.ppat.1004189
• 发表时间: 2014-07
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Giese S;Marsh M
• 通讯作者: Marsh M

Editorial overview - virus entry: towards reality - refining models of virus entry.

编辑概述 - 病毒进入：走向现实 - 完善病毒进入模型。

• DOI: 10.1016/j.coviro.2014.01.001
• 发表时间: 2014
• 期刊: Current opinion in virology
• 影响因子: 5.9
• 作者: Marsh M

Encyclopedia of Cell Biology

细胞生物学百科全书

• DOI: 10.1016/b978-0-12-394447-4.20047-3
• 发表时间: 2016
• 作者: Giese S

A new panel of epitope mapped monoclonal antibodies recognising the prototypical tetraspanin CD81.

• DOI: 10.12688/wellcomeopenres.12058.1
• 发表时间: 2017
• 期刊: Wellcome open research
• 作者: Grove J;Hu K;Farquhar MJ;Goodall M;Walker L;Jamshad M;Drummer HE;Bill RM;Balfe P;McKeating JA
• 通讯作者: McKeating JA