近日，荷兰皇家艺术与科学院教授Marvin E. Tanenbaum团队的研究发现生物分子凝聚种子的预组装驱动RSV复制。这一研究成果于2026年1月28日发表在国际顶尖学术期刊《自然》上。

为了揭示病毒主题如何解决这一悖论以建立VFs，研究小组使用单基因组病毒核糖核蛋白（vRNP）分辨率实时可视化RSV早期感染。他们的结果表明，VFs是通过感染vRNPs而不是在细胞质中重新形成核的。VF的成核进一步需要病毒蛋白蛋白相互作用网络在vRNPs上的病毒粒子预组装，以形成“预复制中心”（PRCs）。PRCs是有效的凝聚核种子，因为它们能有效地招募和保留病毒蛋白。PRCs的高亲和力还导致病毒聚合酶及其辅助因子的关联增加，即使在没有VFs的情况下也能有效地进行病毒转录。这些活动共同形成了一个前馈循环，推动了VF的快速形成。PRC组装依赖于病毒粒子内的病毒蛋白水平，并且在病毒粒子之间具有高度的异质性，这解释了感染进展中的细胞间异质性，并将异质性病毒粒子确定为感染异质性的重要来源。总之，他们的研究结果表明，在进入宿主细胞时，病毒粒子内的PRC预组装启动了病毒凝聚核，并解释了RSV感染的细胞间异质性。

据介绍，在感染过程中，许多RNA病毒主题，包括呼吸道合胞病毒（RSV），形成专门的生物分子凝聚体，病毒工厂（VFs），在那里病毒转录和复制发生。矛盾的是，凝析核通常需要高浓度的蛋白质，但在感染中达到足够的蛋白质水平被认为需要VFs来进行病毒转录和复制。

附：英文原文

Title: Pre-assembly of biomolecular condensate seeds drives RSV replication

Author: Ratnayake, Dhanushika, Galloux, Marie, Boersma, Sanne, Noerenberg, Marko, Sizun, Christina, Sacristan, Carlos, Sourimant, Julien, Lakerveld, Anke J., Gelderloos, Anne T., Apperloo, Leonie, Demyanenko, Yana, Baars, Matthijs J. D., Banerjee, Rupa, Dreier, Birgit, Furler, Sven, Mazur, Natalie I., Bont, Louis J., Mohammed, Shabaz, Plckthun, Andreas, lout, Jean-Franois, Kops, Geert J. P. L., Castello, Alfredo, van Kasteren, Puck B., Rameix-Welti, Marie-Anne, Tanenbaum, Marvin E.

Issue&Volume: 2026-01-28

Abstract: During infection, many RNA viruses, including respiratory syncytial virus (RSV), form specialized biomolecular condensates, viral factories (VFs), where viral transcription and replication occur1,2. Paradoxically, high protein concentrations are typically required for condensate nucleation3, yet attaining sufficient protein levels in infection is thought to require VFs for viral transcription and replication. Here, to uncover how viruses solve this paradox to establish VFs, we visualized early infection of RSV in real time with single genomic viral ribonucleoprotein (vRNP) resolution. Our results reveal that VFs are nucleated from infecting vRNPs rather than de novo in the cytoplasm. VF nucleation further requires in-virion pre-assembly of viral protein–protein interaction networks on vRNPs to form ‘pre-replication centres’ (PRCs). PRCs are potent condensate nucleation seeds due to their efficient recruitment and retention of viral proteins. The high affinity of PRCs also results in increased association of the viral polymerase and its co-factors, allowing efficient viral transcription even in the absence of VFs. Together, these activities create a feed-forward loop that drives rapid VF formation. PRC assembly depends on in-virion viral protein levels and is highly heterogeneous among virions, explaining cell-to-cell heterogeneity in infection progression, and identifying heterogeneous virions as an important origin of infection heterogeneity. Together, our results show that in-virion pre-assembly of PRCs kick-starts viral condensate nucleation upon host-cell entry and explains cell-to-cell heterogeneity in RSV infection.

DOI: 10.1038/s41586-025-10071-5

Source: https://www.nature.com/articles/s41586-025-10071-5