The genetics of virus particle shape in equine influenza A virus.

The genetics of virus particle shape in equine influenza A virus.
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DOI:
10.1111/irv.12197
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发表时间:
2013-12
影响因子:
4.4
通讯作者:
Digard P
Digard P
中科院分区:
医学4区
文献类型:
--
作者:
Elton D;Bruce EA;Bryant N;Wise HM;MacRae S;Rash A;Smith N;Turnbull ML;Medcalf L;Daly JM;Digard P

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许多人类甲型流感病毒株产生高度多形性病毒颗粒,其在极端情况下可以近似为直径约100 nm的球体或具有类似横截面但延长至许多微米长度的细丝。丝状病毒粒子在病毒生命周期中的作用仍然是个谜。在这里,我们开始定义马A型流感病毒中病毒颗粒形状的形态学和遗传学,使用反向遗传学和感染细胞的显微镜检查。发现大多数测试的H3 N8毒株产生丝状病毒体,原型H7 N7 A/eq/布拉格/56毒株也是如此。唯一的例外是原型H3 N8分离株A/eq/迈阿密/63。将来自丝状和非丝状毒株的马流感病毒M基因重配成非丝状人病毒A/PR/8/34,证实片段7是颗粒形状的主要决定因素。序列分析确定了三个M1氨基酸多态性与确定病毒粒子形态学可能相关,并将这些变化引入病毒证实了两个的重要性:S85 N和N231 D。然而,虽然任何一种变化单独影响细丝的生产,最大的影响时,看到的多态性结合引入。因此,来自马宿主的甲型流感病毒也产生丝状病毒体,并且主要的遗传决定簇由M1蛋白设定。然而,精确的序列决定簇与先前在人或猪病毒中鉴定的那些不同。
Many human strains of influenza A virus produce highly pleomorphic virus particles that at the extremes can be approximated as either spheres of around 100 nm diameter or filaments of similar cross‐section but elongated to lengths of many microns. The role filamentous virions play in the virus life cycle remains enigmatic. Here, we set out to define the morphology and genetics of virus particle shape in equine influenza A virus, using reverse genetics and microscopy of infected cells. The majority of H3N8 strains tested were found to produce filamentous virions, as did the prototype H7N7 A/eq/Prague/56 strain. The exception was the prototype H3N8 isolate, A/eq/Miami/63. Reassortment of equine influenza virus M genes from filamentous and non‐filamentous strains into the non‐filamentous human virus A/PR/8/34 confirmed that segment 7 is a major determinant of particle shape. Sequence analysis identified three M1 amino acid polymorphisms plausibly associated with determining virion morphology, and the introduction of these changes into viruses confirmed the importance of two: S85N and N231D. However, while either change alone affected filament production, the greatest effect was seen when the polymorphisms were introduced in conjunction. Thus, influenza A viruses from equine hosts also produce filamentous virions, and the major genetic determinants are set by the M1 protein. However, the precise sequence determinants are different to those previously identified in human or porcine viruses.
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