G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation

到目前为止，全世界已有近1亿例SARS-CoV-2感染病例，其中200多万人死亡。似乎可以肯定的是，这种病毒将在人类群体中永久站稳脚跟，成为地方性疾病，这意味着在可预见的未来，需要采取多种战略和措施来预防、控制和治疗SARS-CoV-2感染。对于所有的病毒感染，在疾病、康复、病毒持久性或继续传播方面的结果取决于病毒复制和感染者的免疫反应之间的平衡。随着SARS-CoV-2继续在人体内传播，这种平衡将随着时间的推移而改变；一方面，来自动物来源的病毒可能会进一步适应其新的人类宿主，另一方面，人类群体中的获得性免疫反应将积累起来，潜在地限制病毒的传播。具有基因组突变的新的SARS CoV-2变种(不同的“基因”)将出现，其中一些可能改变了生物学特性(“表型”)：包括更容易在人与人之间传播，加剧或减轻疾病和死亡，传播到其他动物物种(以建立非人类宿主)，或逃避通过自然感染或疫苗获得的人类免疫。鉴于由于高病毒传播率和疫苗接种计划，人口免疫力正在提高，后者在目前是一个特别令人关切的问题。SARS-CoV-2的许多变种现在正在全球出现，对它们对社会构成的风险的合理评估需要对生物特性的任何引起变化的循证科学理解。英国国家病毒学联盟(G2P-UK)将利用10个领先研究中心的病毒学专业知识，开展一系列定向和互补性的实验测试，将SARS-CoV-2序列变异与病毒行为和功能联系起来，从而解决这一关键的知识差距。测试将包括使用一系列实验室感染模型详细评估病毒生长，病毒对包括抗体在内的人类免疫机制抑制的敏感性，评估单个病毒蛋白质的功能，以及使用已建立的小动物模型评估病毒的繁殖和传播性。G2P内部的协调将通过预先商定的方法和标准、材料、标本和技术的自由交换、定期科学会议和专门的联盟网站来实现。需要重点调查的令人担忧的SARS-CoV-2变种将通过与另一个财团COG-UK的科学家协调工作来优先考虑，后者负责病毒监测和跟踪新出现的病毒变种。G2P还将与其他关键的英国组织和科学财团密切合作，包括英国公共卫生实验室和英国冠状病毒免疫联盟(CIC)，以及在英国和国际上工作的其他领导小组，以收集对令人担忧的变体的生物学表型及其相关风险的最全面和最深入的评估。这些结论将迅速和公开地与Nervtag和SAGE等关键群体分享，为国家大流行管理和患者治疗、诊断、人口水平监测、感染控制和疫苗接种战略提供信息。

There have been almost 100 million cases of SARS-CoV-2 infections world-wide, with more than two million deaths to date. It seems certain that this virus will permanently establish itself in the human population and become endemic, meaning that multiple strategies and measures will be needed to prevent, control and treat SARS-CoV-2 infections for the foreseeable future. For all viral infections, the outcomes in terms of disease, recovery, viral persistence or onward transmission are dictated by the balance between virus replication and the immune responses of the infected individuals. As SARS-CoV-2 continues to circulate in people this balance will change over time; On one hand the virus that emerged from an animal source may further adapt to its new human host and on the other hand the acquired immune response in the human population will accumulate potentially limiting viral spread.New variants of SARS CoV-2 with mutations in the genome (different 'genotype') will emerge and some may have altered biological properties ("phenotype"): including transmitting between humans more readily, exacerbating or attenuating disease and mortality, spreading to other animal species (to establish non-human reservoirs) or evading human immunity that is acquired through natural infection or vaccination. The latter is a particular concern at this moment in time given that population-level immunity is increasing as a result of high virus circulation and vaccination programs. Many variants of SARS-CoV-2 are now appearing globally, and the rational assessment of the risks they pose to society requires an evidence-based scientific understanding of any causative changes in biological properties. The Genotype-to-Phenotype UK National Virology Consortium (G2P-UK) will address this critical knowledge gap by leveraging the combined virological expertise of ten leading research centres to undertake a suite of directed and complementary experimental tests that will link SARS-CoV-2 sequence variation to virus behaviour and function. Tests will include the detailed assessments of virus growth using a series of laboratory models of infection, susceptibility of viruses to inhibition by human immune mechanisms including antibodies, evaluations of the functionality of individual virus proteins, and virus propagation and transmissibility using established small animal models. Co-ordination within G2P will be achieved through upfront agreed methodologies and standards, the free exchange of materials, specimens and know-how, regular scientific meetings and a dedicated consortium website. SARS-CoV-2 variants of concern that warrant focused investigation will be prioritised through co-ordinated workings with scientists at another consortium, COG-UK, who are responsible for virus surveillance and keeping track of emerging virus variants. Variants of concern will be selected on criteria that include altered disease outcomes, rapid emergence or spread, infections in the context of pre-existing immunity, apparent or inferred escape from immunity, or resistance to anti-viral drugs.G2P will also engage closely with other key UK organisations and scientific consortia including UK-wide Public Health laboratories and UK-CIC (Coronavirus Immunology Consortium), as well as other leading groups working in the UK and internationally, to gather the most holistic and incisive evaluation of the biological phenotypes of variants of concern and the associated risks they carry. These conclusions will be shared rapidly and openly with key groups such as NERVTAG and SAGE to inform national pandemic management and strategies for patient treatment, diagnostics, population-level surveillance, infection control and vaccination.