Subedi Sushma, Nag Niharika, Shukla Harish, Padhi Aditya K, Tripathi Timir
Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, India.
Laboratory for Computational Biology & Biomolecular Design, School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi, India.
J Cell Biochem. 2024 Dec;125(12):e30480. doi: 10.1002/jcb.30480. Epub 2023 Oct 5.
In recent years, it has been shown that the liquid-liquid phase separation (LLPS) of virus proteins plays a crucial role in their life cycle. It promotes the formation of viral replication organelles, concentrating viral components for efficient replication and facilitates the assembly of viral particles. LLPS has emerged as a crucial process in the replication and assembly of herpes simplex virus-1 (HSV-1). Recent studies have identified several HSV-1 proteins involved in LLPS, including the myristylated tegument protein UL11 and infected cell protein 4; however, a complete proteome-level understanding of the LLPS-prone HSV-1 proteins is not available. We provide a comprehensive analysis of the HSV-1 proteome and explore the potential of its proteins to undergo LLPS. By integrating sequence analysis, prediction algorithms and an array of tools and servers, we identified 10 HSV-1 proteins that exhibit high LLPS potential. By analysing the amino acid sequences of the LLPS-prone proteins, we identified specific sequence motifs and enriched amino acid residues commonly found in LLPS-prone regions. Our findings reveal a diverse range of LLPS-prone proteins within the HSV-1, which are involved in critical viral processes such as replication, transcriptional regulation and assembly of viral particles. This suggests that LLPS might play a crucial role in facilitating the formation of specialized viral replication compartments and the assembly of HSV-1 virion. The identification of LLPS-prone proteins in HSV-1 opens up new avenues for understanding the molecular mechanisms underlying viral pathogenesis. Our work provides valuable insights into the LLPS landscape of HSV-1, highlighting potential targets for further experimental validation and enhancing our understanding of viral replication and pathogenesis.
近年来，研究表明病毒蛋白的液-液相分离（LLPS）在其生命周期中起着至关重要的作用。它促进病毒复制细胞器的形成，浓缩病毒成分以实现高效复制，并促进病毒颗粒的组装。LLPS已成为单纯疱疹病毒1型（HSV-1）复制和组装中的关键过程。最近的研究已经确定了几种参与LLPS的HSV-1蛋白，包括肉豆蔻酰化的被膜蛋白UL11和感染细胞蛋白4；然而，目前还没有对易于发生LLPS的HSV-1蛋白进行完整的蛋白质组水平的了解。我们对HSV-1蛋白质组进行了全面分析，并探索了其蛋白质发生LLPS的潜力。通过整合序列分析、预测算法以及一系列工具和服务器，我们确定了10种具有高LLPS潜力的HSV-1蛋白。通过分析易于发生LLPS的蛋白的氨基酸序列，我们确定了在易于发生LLPS的区域中常见的特定序列基序和富集的氨基酸残基。我们的研究结果揭示了HSV-1中多种易于发生LLPS的蛋白，它们参与了诸如复制、转录调控和病毒颗粒组装等关键病毒过程。这表明LLPS可能在促进特殊病毒复制区室的形成和HSV-1病毒体的组装中起关键作用。HSV-1中易于发生LLPS的蛋白的鉴定为理解病毒发病机制的分子机制开辟了新途径。我们的工作为HSV-1的LLPS格局提供了有价值的见解，突出了有待进一步实验验证的潜在靶点，并增进了我们对病毒复制和发病机制的理解。
