Quantifying the risk of pandemic influenza virus evolution by mutation and re-assortment
Quantifying the risk of pandemic influenza virus evolution by mutation and re-assortment
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DOI：
10.1016/j.vaccine.2015.10.056
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发表时间：
2015-12-08
期刊：
影响因子：
5.5
通讯作者：
Osterhaus, Albert D. M. E.
中科院分区：
文献类型：
--
作者：
Reperant, Leslie A.;Grenfell, Bryan T.;Osterhaus, Albert D. M. E.
人畜共患甲型流感病毒（IAV）感染的大规模爆发可能预示着流感大流行。然而，在人畜共患感染或与人畜共患和季节性IAV共感染后，空气传播变异演变的可能性仍然知之甚少，在此过程中累积突变与重配的相对重要性也知之甚少。使用离散时间概率模型，我们确定了定量的概率范围内，1-5个突变的传染性变异和传染性回复进化后，一定数量的人畜共患IAV感染。对大量模型参数值的系统探索旨在考虑流感病毒感染、流行病学和进化过程中的不确定性和可变性。这些模型表明，免疫功能低下的个体通过突变的积累而产生具有大流行潜力的IAV变体的风险很高。然而，免疫活性和免疫功能低下的个体都可以产生高病毒载量的单突变体和双突变体，这可能有助于它们的向前传播和随后在新感染个体中积累额外的1-2个突变。这可能导致完全可传播的基因型沿着接触传播的短链沿着进化。虽然人畜共患和季节性IAV的合并感染被证明是罕见的事件，但它始终导致高病毒载量的回复剂，这可能有助于它们在人类之间的进一步传播。预防或限制免疫功能低下和接触者（包括卫生保健工作者）中的人畜共患IAV感染，以及针对季节性IAV的疫苗接种限制合并感染的风险，应被视为通过突变和重配的积累来阻止新型大流行IAV演变的基本工具。(C)2015作者爱思唯尔有限公司出版
Large outbreaks of zoonotic influenza A virus (IAV) infections may presage an influenza pandemic. However, the likelihood that an airborne-transmissible variant evolves upon zoonotic infection or co-infection with zoonotic and seasonal IAVs remains poorly understood, as does the relative importance of accumulating mutations versus re-assortment in this process. Using discrete-time probabilistic models, we determined quantitative probability ranges that transmissible variants with 1-5 mutations and transmissible re-assortants evolve after a given number of zoonotic IAV infections. The systematic exploration of a large population of model parameter values was designed to account for uncertainty and variability in influenza virus infection, epidemiological and evolutionary processes. The models suggested that immunocompromised individuals are at high risk of generating IAV variants with pandemic potential by accumulation of mutations. Yet, both immunocompetent and immunocompromised individuals could generate high viral loads of single and double mutants, which may facilitate their onward transmission and the subsequent accumulation of additional 1-2 mutations in newly-infected individuals. This may result in the evolution of a full transmissible genotype along short chains of contact transmission. Although co-infection with zoonotic and seasonal IAVs was shown to be a rare event, it consistently resulted in high viral loads of re-assortants, which may facilitate their onward transmission among humans. The prevention or limitation of zoonotic IAV infection in immunocompromised and contact individuals, including health care workers, as well as vaccination against seasonal IAVs limiting the risk of co-infection should be considered fundamental tools to thwart the evolution of a novel pandemic IAV by accumulation of mutations and re-assortment. (C) 2015 The Authors. Published by Elsevier Ltd.