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

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-11-01 DOI:10.1016/j.antiviral.2024.106023
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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.
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呼吸道合胞病毒的新型细胞间传播模式有助于中和逃逸。
尽管最近批准了两种针对老年人的前 F 疫苗,但开发广泛使用的呼吸道合胞病毒(RSV)疫苗仍是一项重大挑战。以前的报告表明,即使疫苗诱导免疫产生了针对前 F 蛋白的高滴度强效中和抗体,也可能无法完全抑制 RSV 的突破性感染。这种对 RSV 突破性感染的不完全抑制会导致接种疫苗的人患呼吸道疾病(ERD)的风险增加。强效中和抗体不能完全阻止 RSV 突破性感染的原因尚不清楚。为了解释这一现象,我们研究了强效中和抗体对 RSV 细胞间传播的影响。我们的研究结果表明,特定滴度的强效中和抗体(如 5C4)可以阻止某些细胞间传播方式,如无细胞病毒的扩散和病毒通过丝状体的传递。然而,这些抗体并不能完全抑制整个细胞间传播过程。通过使用超分辨率成像技术,我们观察到了一种新颖高效的传播模式,即病毒物质通过细胞间纳米管的过渡(TVMIN),它独立于病毒,对抗体的存在不敏感。TVMIN允许RSV感染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细胞。TVMIN 早在感染后 5 小时(h.p.i.)就开始发挥作用,并迅速引发受体细胞感染。我们的数据为研究 RSV 的细胞间传播提供了新的视角,可能有助于解释突破性感染的发生。
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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