Neuraminidase Activity Modulates Cellular Coinfection during Influenza A Virus Multicycle Growth.

Neuraminidase Activity Modulates Cellular Coinfection during Influenza A Virus Multicycle Growth.
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DOI:
10.1128/mbio.03591-22
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发表时间:
2023-06-27
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学1区
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单个细胞被多个病毒体感染在许多病毒的复制和传播中起着关键作用,但在多细胞病毒生长期间控制细胞共感染的机制仍不清楚。在这里,我们调查病毒的内在因素,控制细胞合并感染的甲型流感病毒(IAV)。使用定量荧光跟踪病毒粒子从单个感染细胞的传播,我们确定IAV表面蛋白神经氨酸酶(NA)作为细胞共感染的关键决定因素。我们将这种效应映射到NA从感染细胞和邻近未感染细胞中耗尽病毒受体的能力。在病毒感染潜力低的情况下,NA的遗传或药理学抑制通过增加邻近细胞接受的病毒载量来增加感染的局部扩散。这些结果确定了病毒的内在因素,有助于细胞的感染多样性,并建议NA活性的最佳水平取决于病毒的感染潜力的问题。
Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA’s ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic or pharmacological inhibition of NA increases the local spread of infection by increasing the viral load received by neighboring cells. These results identify virus-intrinsic factors that contribute to cellular multiplicity of infection and suggest that optimal levels of NA activity depend on the infectious potential of the virus in question.
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