时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Article TRAP complex is essential for coronavirus replication and glycoprotein biogeneses Yihan Tian 1,2 , Junchao Shi 1,2 , Shaoqian Mu1 , Hanlu Wei1 , Wenqi He 1 & Zi Li 1 Abstract Coronaviruses remodel the endoplasmic reticulum (ER) to build replication organelles while producing heavily glycosylated mem- brane proteins, but the mechanisms coordinating these demands are unclear.；However, it remains unresolved how coronaviruses couple large-scale ER membrane remodeling to the simultaneous production, translocation, and maturation of their heavily glycosylated membrane proteins within the same organelle.；These parallel demands imply that coronaviruses co-opt specific host factors to synchronize protein biogenesis with membrane reorganization, yet the key host machinery linking these processes remains unknown.
方法
To define the temporal sequence of RO biogenesis, we performed a time-course analysis in PHEV-infected N2a cells integrating replication marker profiling with ultrastructural exam- ination.；Genome-wide CRISPR screen identifies TRAPγ as an essential host factor for PHEV replication To systematically identify host factors required for PHEV infection, we performed a genome-wide CRISPR loss-of-function screen in N2a neuroblastoma cells (Fig. 2A).；Raw sequencing data from this screen have been deposited in the NCBI Sequence Read Archive (SRA) under accession number PRJNA1484813.；Consis- tently, infectious virus production was strongly diminished in TRAPγ KO cells, as measured by plaque assay and TCID50 analysis (Fig. 2I,J).
核心结论
Using porcine hemagglutinating encephalomyelitis virus (PHEV) as a model, we identify TRAPγ in a genome-wide CRISPR-Cas9 screen as essential for productive viral infection.；Viral glycoproteins (nsp4, Spike, and hemagglutinin-esterase) selectively engage specific TRAP subunits (α, β, γ, and δ), and reducing their signal-sequence hydrophobicity compromises glycoprotein production and N-gly- cosylation, consistent with impaired co-translational ER targeting or translocation.；The ER utilizes two primary pathways for protein translocation: co-translational and post-translational mechanisms (Schnell and Hebert 2003; Reid and Nicchitta, 2012; Schwarz and Blower, 2016). ‖ 结论：The eluted samples, together with the input controls, were then resolved by SDS‑PAGE and subjected to immunoblotting with the indicated antibodies.
局限
Despite coronaviruses are known to exploit ER plasticity (Hou et al, 2023; Sun et al, 2023; Zhang et al, 2021), whether TRAP functions as a limiting host determinant for coronavirus infection and whether it contributes beyond viral proteostasis to de novo replication organelle biogenesis has not been systematically addressed.；EMBO reports Yihan Tian et al 10 EMBO reports © The Author(s) subsequent TRAP-assisted translocation, thereby limiting produc- tive membrane protein biogenesis rather than leading to accumula- tion of stable cytosolic precursors.；Future studies should focus on resolving the structural basis of TRAP-glycoprotein interactions through high- resolution approaches such as cr
对本项目的价值
★☆☆☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。
全文来源
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原文题录
- 英文标题：TRAP complex is essential for coronavirus replication and glycoprotein biogeneses.
- 期刊与标识：EMBO Rep · PMID 42957879 · DOI 10.1038/s44319-026-00986-z
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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