Understanding influenza A virus: linking transmission, evolutionary dynamics, pathogenesis and immunity in pigs

了解甲型流感病毒：将猪的传播、进化动力学、发病机制和免疫联系起来

• 批准号: BB/L001330/1
• 负责人: Bryan Charleston
• 金额: $ 567万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL001330%2F1
• 关键词: Understanding; influenza; virus; linking; transmission

Swine influenza attracts considerable attention because of the threat of zoonotic infections causing human pandemics. During the pandemic, a fear that viruses emerging from pigs may infect people resulted in the widespread destruction of animals in some countries and trade bans. Consequently, the insidious effects of this highly prevalent virus on the health and welfare of pig populations, estimated to increase the cost of production by £7 per finished pig, have not been given due regard. The primary disease caused by influenza virus in usually mild, but results in greater susceptibility to secondary infections. Vaccination will be a key control measure for influenza in pigs to improve general herd health.Through our studies we will develop a more detailed understanding of the dynamics of virus transmission and the consequences of transmission and vaccination in driving viral evolution. During these studies we will also define a range of parameters, for example local and systemic immune responses and sites of virus replication, which are associated with the onset and cessation of transmission. We need to know if current and proposed novel vaccines not only prevent clinical signs but also stop viruses being transmitted unnoticed. Furthermore, if viruses can be transmitted unnoticed are they changing because of the immune response in the population? To answer these questions we need to understand virus transmission in detail and how the viruses change when they pass between animals. We can then apply this new knowledge to population wide models of disease spread to predict the efficiency of any proposed control measures. This knowledge will also inform the design of novel vaccines.Vaccination against influenza in pigs is not routinely performed in Europe mainly for two reasons: the cost benefit of vaccination has not been clearly demonstrated and it is not clear that the available vaccines will protect against the strains currently circulating in the pig population. The most striking example of the latter is that current vaccines do not include pandemic H1N1 influenza virus antigen.These studies will provide essential evidence to design control programmes for influenza in pigs, most notably: i) finding out how efficient are the current prophylactic methods at controlling the spread of infection; ii) what level of immunity is required in a population to prevent the spread of infection and the evolution of new strains of virus and iii) determine whether new, broadly cross protective vaccines are more effective at controlling influenza infections in swine to enhance animal health and livestock production.Importantly, this type of information is not available for any natural mammalian hosts of influenza viruses, including humans and horses. Therefore, the results of our studies will have a broad impact on influenza control measures.

由于人畜共患感染可能导致人类大流行，猪流感引起了广泛关注。在大流行期间，由于担心猪身上出现的病毒可能感染人类，导致一些国家对动物进行了大范围的破坏并实施了贸易禁令。因此，这种高度流行的病毒对猪群健康和福利的潜在影响（估计每头成品猪的生产成本增加 7 英镑）尚未得到应有的重视。流感病毒引起的原发病通常较轻，但更容易继发感染。疫苗接种将是控制猪流感、改善猪群整体健康的关键措施。通过我们的研究，我们将更详细地了解病毒传播的动态以及传播和疫苗接种对病毒进化的影响。在这些研究中，我们还将定义一系列参数，例如与传播的开始和停止相关的局部和全身免疫反应以及病毒复制位点。我们需要知道当前和拟议的新型疫苗是否不仅可以预防临床症状，还可以阻止病毒在未被注意到的情况下传播。此外，如果病毒可以在不被注意的情况下传播，它们是否会因为人群的免疫反应而发生变化？为了回答这些问题，我们需要详细了解病毒传播以及病毒在动物之间传播时如何变化。然后，我们可以将这些新知识应用于疾病传播的人群模型，以预测任何拟议控制措施的效率。这些知识还将为新型疫苗的设计提供信息。在欧洲，猪流感疫苗接种并未常规进行，主要有两个原因：疫苗接种的成本效益尚未得到明确证明，并且尚不清楚现有疫苗是否能够预防目前在猪群中流行的病毒株。后者最引人注目的例子是，当前的疫苗不包含大流行性 H1N1 流感病毒抗原。这些研究将为设计猪流感控制方案提供必要的证据，最值得注意的是： i) 找出当前预防方法在控制感染传播方面的效率如何； ii) 人群需要什么水平的免疫力来防止感染传播和新病毒株的进化，以及 iii) 确定新的、广泛交叉保护的疫苗是否能更有效地控制猪的流感感染，以增强动物健康和牲畜生产。重要的是，此类信息不适用于流感病毒的任何天然哺乳动物宿主，包括人类和马。因此，我们的研究结果将对流感控制措施产生广泛的影响。

项目成果

Statistical modelling of data showing pandemic H1N1 2009 swine influenza a virus infection kinetics in vaccinated pigs.

显示 2009 年 H1N1 甲型流感病毒在已接种疫苗的猪中的感染动力学的数据统计模型。

• DOI: 10.1016/j.dib.2019.104576
• 发表时间: 2019
• 期刊: Data in brief
• 影响因子: 1.2
• 作者: Canini L

H1N1 (09pdm) transmission parameters and host response in naïve pigs

H1N1 (09pdm) 传播参数和宿主对幼猪的反应

• 发表时间: 2015
• 作者: Aramouni, M

A pharmacokinetic/viral kinetic model to evaluate treatment of chronic HCV infection with a non-nucleoside polymerase inhibitor.

• DOI: 10.3851/imp3216
• 发表时间: 2018
• 期刊: Antiviral therapy
• 影响因子: 1.2
• 作者: Canini L;Lemenuel-Diot A;Brennan BJ;Smith PF;Perelson AS
• 通讯作者: Perelson AS

Biased phylodynamic inferences from analysing clusters of viral sequences

通过分析病毒序列簇得出的有偏差的系统动力学推论

• DOI: 10.1101/095661
• 发表时间: 2016
• 作者: Dearlove B

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir.

HCV动力学和建模分析表明，与Daclatasvir，Simeprevir或Ledipasvir之间的Sofosbuvir组合方案之间的治疗时间相似。

• DOI: 10.1016/j.jhep.2016.02.022
• 发表时间: 2016-06
• 期刊: Journal of hepatology
• 影响因子: 25.7
• 作者: Dahari H;Canini L;Graw F;Uprichard SL;Araújo ES;Penaranda G;Coquet E;Chiche L;Riso A;Renou C;Bourliere M;Cotler SJ;Halfon P
• 通讯作者: Halfon P