Discovery and characterization of swine host factors required to support swine influenza virus replication.

支持猪流感病毒复制所需的猪宿主因子的发现和表征。

• 批准号: BB/R013071/1
• 负责人: Wendy Barclay
• 金额: $ 52.71万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR013071%2F1
• 关键词: Discovery; characterization; swine; host; factors

Infection of pigs with influenza viruses is a problem both for animal and human health. Swine influenza virus infections cause production losses and can predispose to more serious complications leading to loss of stock. Moreover infections of pigs by avian influenza viruses can pre-empt the emergence of a novel influenza virus that infects humans. Indeed the last influenza pandemic in 2009 had its most recent origin in pigs. Pork is an important protein source for the developed and developing world. China is a major pig producer, where pigs are reared in large holdings under sometimes crowded conditions; a perfect breeding ground for the evolution and emergence of new strains of virus. The high population in China, its geography and its climate make it a hotspot for emergence of influenza viruses. One future solution to these threats is to employ recent developments in gene editing to make a pig that is resistant to infection with influenza viruses. This is not so far-fetched; indeed, pigs resistant to another pig virus called PRRS were recently generated. However, in order to apply the breakthrough to the influenza problem we need to identify which genes in the pigs should be altered to stop the virus from being able to infect, and then define precisely how to alter them so that there is as little disruption to the meat production and breeding capacity in the edited animals.We will identify the pig genes that are co-opted by swine influenza viruses to support their replication using a novel screening method, in pig cells with authentic swine influenza viruses typical of those circulating in China today. Then we will employ another novel screening method to work out the least changes we can make in the pig gene in order to stop the virus from infecting, because we reason this minimalistic and precise editing strategy will be the most acceptable to consumers and farmers alike.

猪感染流感病毒对动物和人类健康都是一个问题。猪流感病毒感染会造成产量损失，并可能导致更严重的并发症，导致牲畜损失。此外，禽流感病毒对猪的感染可以预先阻止感染人类的新型流感病毒的出现。事实上，2009年的上一次流感大流行最近一次起源于猪。猪肉是发达国家和发展中国家的重要蛋白质来源。中国是一个主要的生猪生产国，在有时拥挤的条件下大量饲养生猪;这是新病毒株进化和出现的完美温床。中国人口众多，地理和气候使其成为流感病毒出现的热点。未来应对这些威胁的一个解决方案是利用基因编辑的最新进展，使猪对流感病毒的感染具有抵抗力。这并不是那么牵强;事实上，最近已经产生了对另一种称为PRRS的猪病毒具有抵抗力的猪。然而，为了将这一突破应用于流感问题，我们需要确定应该改变猪的哪些基因以阻止病毒感染，然后精确地定义如何改变它们，以便对编辑后的动物的肉类生产和繁殖能力造成尽可能小的破坏。我们将识别出猪的基因，选择的猪流感病毒，以支持他们的复制使用新的筛选方法，在猪细胞与真正的猪流感病毒的典型那些在中国今天流行。然后，我们将采用另一种新的筛选方法，找出我们可以在猪基因中做出的最小改变，以阻止病毒感染，因为我们认为这种最简单和精确的编辑策略将是消费者和农民最容易接受的。

项目成果

An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization.

• DOI: 10.1038/s41467-023-41308-4
• 发表时间: 2023-10-10
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Sheppard, Carol M.;Goldhill, Daniel H.;Swann, Olivia C.;Staller, Ecco;Penn, Rebecca;Platt, Olivia K.;Sukhova, Ksenia;Baillon, Laury;Frise, Rebecca;Peacock, Thomas P.;Fodor, Ervin;Barclay, Wendy S.
• 通讯作者: Barclay, Wendy S.

A natural variant in ANP32B impairs influenza virus replication in human cells.

• DOI: 10.1099/jgv.0.001664
• 发表时间: 2021-09
• 期刊: The Journal of general virology
• 作者: Staller E;Sheppard CM;Baillon L;Frise R;Peacock TP;Sancho-Shimizu V;Barclay WS
• 通讯作者: Barclay WS

A common TMPRSS2 variant has a protective effect against severe COVID-19.

• DOI: 10.1016/j.retram.2022.103333
• 发表时间: 2022-05
• 期刊: Current research in translational medicine
• 影响因子: 4.1
• 作者: David A;Parkinson N;Peacock TP;Pairo-Castineira E;Khanna T;Cobat A;Tenesa A;Sancho-Shimizu V;GenOMICC Consortium;ISARIC4C Investigators;Casanova JL;Abel L;Barclay WS;Baillie JK;Sternberg MJ
• 通讯作者: Sternberg MJ

Mammalian ANP32A and ANP32B proteins drive alternative avian influenza virus polymerase adaptations

• DOI: 10.1101/2020.09.03.282384
• 发表时间: 2020-09
• 期刊: bioRxiv
• 作者: T. Peacock;C. Sheppard;E. Staller;R. Frise;Olivia C. Swann;Daniel H. Goldhill;Jason S. Long;W. Barclay

Mammalian ANP32A and ANP32B Proteins Drive Differential Polymerase Adaptations in Avian Influenza Virus.

• DOI: 10.1128/jvi.00213-23
• 发表时间: 2023-05-31
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Peacock, Thomas P.;Sheppard, Carol M.;Lister, Margaret G.;Staller, Ecco;Frise, Rebecca;Swann, Olivia C.;Goldhill, Daniel H.;Long, Jason S.;Barclay, Wendy S.
• 通讯作者: Barclay, Wendy S.