Influenza A virus is a serious human pathogen that assembles enveloped virions on the plasma membrane of the host cell. The pleiomorphic morphology of influenza A virus, represented by spherical, elongated, or filamentous particles, is important for the spread of the virus in nature. Using fixative protocols for sample preparation and negative staining electron microscopy, we found that the recombinant A/WSN/33 (H1N1) (rWSN) virus, a strain considered to be strictly spherical, may produce filamentous particles when amplified in the allantoic cavity of chicken embryos. In contrast, the laboratory WSN strain and the rWSN virus amplified in Madin–Darby canine kidney cells exhibited a spherical morphology. Next-generation sequencing (NGS) suggested a rare Ser126Cys substitution in the M1 protein of rWSN, which was confirmed by the mass spectrometric analysis. No structurally relevant substitutions were found by NGS in other proteins of rWSN. Bioinformatics algorithms predicted a neutral structural effect of the Ser126Cys mutation. The mrWSN_M1_126S virus generated after the introduction of the reverse Cys126Ser substitution exhibited a similar host-dependent partially filamentous phenotype. We hypothesize that a shortage of some as-yet-undefined cellular components involved in virion budding and membrane scission may result in the appearance of filamentous particles in the case of usually “nonfilamentous” virus strains.

中文翻译：

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丝状与球形形态：重组 A/WSN/33 (H1N1) 病毒的案例研究

甲型流感病毒是一种严重的人类病原体，它在宿主细胞的质膜上组装有包膜的病毒粒子。甲型流感病毒的多形性形态，以球形、细长或丝状颗粒为代表，对于病毒在自然界中的传播很重要。使用用于样品制备和负染色电子显微镜的固定方案，我们发现重组 A/WSN/33 (H1N1) (rWSN) 病毒，一种被认为是严格球形的毒株，在鸡的尿囊腔中扩增时可能会产生丝状颗粒胚胎。相比之下，实验室 WSN 毒株和在 Madin-Darby 犬肾细胞中扩增的 rWSN 病毒表现出球形形态。下一代测序 (NGS) 表明 rWSN 的 M1 蛋白中存在罕见的 Ser126Cys 取代，质谱分析证实了这一点。NGS 在 rWSN 的其他蛋白质中未发现结构相关的取代。生物信息学算法预测了 Ser126Cys 突变的中性结构效应。在引入反向 Cys126Ser 替代后产生的 mrWSN_M1_126S 病毒表现出类似的宿主依赖性部分丝状表型。我们假设在通常“非丝状”病毒株的情况下，缺乏一些与病毒粒子出芽和膜分裂有关的尚未确定的细胞成分可能导致丝状颗粒的出现。在引入反向 Cys126Ser 替代后产生的 mrWSN_M1_126S 病毒表现出类似的宿主依赖性部分丝状表型。我们假设在通常“非丝状”病毒株的情况下，缺乏一些与病毒粒子出芽和膜分裂有关的尚未确定的细胞成分可能导致丝状颗粒的出现。在引入反向 Cys126Ser 替代后产生的 mrWSN_M1_126S 病毒表现出类似的宿主依赖性部分丝状表型。我们假设在通常“非丝状”病毒株的情况下，缺乏一些与病毒粒子出芽和膜分裂有关的尚未确定的细胞成分可能导致丝状颗粒的出现。