呼吸道合胞病毒的新型细胞间传播方式有助于逃逸中和作用。

Novel intercellular spread mode of respiratory syncytial virus contributes to neutralization escape.

机构信息

State Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.

The First Affiliated Hospital of Xiamen University, Xiamen, China.

出版信息

Antiviral Res. 2024 Nov;231:106023. doi: 10.1016/j.antiviral.2024.106023. Epub 2024 Nov 1.

Abstract

Developing widely used respiratory syncytial virus (RSV) vaccines remains a significant challenge, despite the recent authorization of two pre-F vaccines for elderly adults. Previous reports have suggested that even when vaccine-induced immunity generates high titers of potent neutralizing antibodies targeting the pre-F protein, it may not fully inhibit breakthrough of RSV infections. This incomplete inhibition of RSV breakthrough infections can lead to an increased risk of enhanced respiratory disease (ERD) in vaccinated individuals. The reasons why potent neutralizing antibodies cannot fully prevent RSV breakthrough infections are not yet clear. In an attempt to explain this phenomenon, we investigated the effect of potent neutralizing antibodies on the intercellular spread of RSV. Our findings indicated that a specific titer of potent neutralizing antibodies, such as 5C4, could block certain modes of intercellular spread, such as the diffusion of cell-free virions and the delivery of virions through filopodia. However, these antibodies did not fully inhibit the entire process of intercellular spread. Through the use of super-resolution imaging techniques, we observed a novel and efficient spread mode called the transition of viral materials through intercellular nanotubes (TVMIN), independent of virions and insensitive to the presence of antibodies. TVMIN allowed RSV-infected cells to directly transfer viral materials to neighboring cells via intercellular nanotubes that are rich in microfilaments. TVMIN began as early as 5 h post-infection (h.p.i.) and rapidly initiated infection in recipient cells. Our data provided new insights into the intercellular spread of RSV and might help explain the occurrence of breakthrough infections.

摘要

开发广泛使用的呼吸道合胞病毒 (RSV) 疫苗仍然是一个重大挑战,尽管最近批准了两种针对老年人的前 F 疫苗。以前的报告表明,即使疫苗诱导的免疫产生针对前 F 蛋白的高滴度有效中和抗体,它也可能不能完全抑制 RSV 感染的突破。这种 RSV 突破感染的不完全抑制会导致接种者发生增强型呼吸道疾病 (ERD) 的风险增加。有效中和抗体不能完全预防 RSV 突破感染的原因尚不清楚。为了解释这一现象,我们研究了有效中和抗体对 RSV 细胞间传播的影响。我们的研究结果表明,特定滴度的有效中和抗体(如 5C4)可以阻断某些细胞间传播方式,如无细胞病毒粒子的扩散和通过丝状伪足传递病毒粒子。然而,这些抗体并不能完全抑制细胞间传播的整个过程。通过使用超分辨率成像技术,我们观察到一种新的、有效的传播模式,称为通过细胞间纳米管的病毒物质转移(TVMIN),它独立于病毒粒子,并且对抗体的存在不敏感。TVMIN 允许 RSV 感染的细胞通过富含微丝的细胞间纳米管直接将病毒物质转移到邻近的细胞。TVMIN 早在感染后 5 小时(h.p.i.)就开始,并迅速在受感染的细胞中引发感染。我们的数据提供了关于 RSV 细胞间传播的新见解,并可能有助于解释突破感染的发生。

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