Swine ANP32A supports avian influenza virus polymerase
Swine ANP32A supports avian influenza virus polymerase
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猪 ANP32A 支持禽流感病毒聚合酶
DOI：
10.1101/2020.01.24.916916
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Peacock T
中科院分区：
文献类型：
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作者：
Peacock T
禽流感病毒偶尔会感染和适应哺乳动物，包括人类。猪通常被描述为“混合容器”，对禽源和人源病毒都敏感，这使得出现新的抵抗物，如2009年H1N1大流行的前兆。ANP 32蛋白是作为流感病毒聚合酶辅因子的宿主因子。在这项研究中，我们描述了猪ANP 32 A，独特的哺乳动物ANP 32蛋白测试，支持禽流感病毒聚合酶和禽流感病毒复制的活动。我们进一步表明，在猪源性流感病毒出现在人类中并导致2009年大流行后，它进化了聚合酶基因突变，使其能够更有效地利用人类ANP 32蛋白。我们将猪ANP32A增强的前病毒活性映射到富含亮氨酸的重复序列和中心结构域中的一对氨基酸106和156，并显示这些突变增强了与流感病毒三聚体聚合酶的结合。这些发现有助于阐明猪混合容器特征的分子基础，并进一步加深我们对病毒在这种宿主中的进化和生态学的理解。重要信息禽流感病毒可以从野生鸟类和家禽跳跃到哺乳动物物种，如人类或猪，但只有当它们积累了哺乳动物适应性突变时，它们才能继续传播。猪似乎对禽流感和人类流感毒株都特别敏感，通常被描述为病毒“混合容器”。在这项研究中，我们描述了负责调节病毒复制的宿主因子ANP 32A在猪和人之间的差异。猪ANP32A允许更大范围的流感病毒，特别是来自鸟类的流感病毒复制。它通过比人类版本的蛋白质更紧密地结合病毒聚合酶来做到这一点。这项工作有助于解释猪作为混合容器的独特性质。
Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as “mixing vessels,” being susceptible to both avian- and human-origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study, we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports the activity of avian-origin influenza virus polymerases and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic, it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced proviral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the mixing vessel trait of swine and further our understanding of the evolution and ecology of viruses in this host.IMPORTANCEAvian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but they only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus “mixing vessels.” In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this by binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as mixing vessels.