Areca palm velarivirus 1 encoded P25 hijacks host eIF4E and enhances viral translation through strengthening the interaction of eIF4E with 3′ cap-independent translation enhancer

(2026) 8:24 Wan et al. Phytopathology Research https://doi.org/10.1186/s42483-025-00409-2 Phytopathology Research Open Access RESEARCH Areca palm velarivirus 1 encoded P25 hijacks host eIF4E and enhances viral translation through strengthening the interaction of eIF4E with 3′ cap‑independent translation enhancer Siyu Wan1, Hongxing Wang1* and Xi Huang1* Abstract Plant viruses employ diverse strategies to hijack host machinery for viral translation initiation. Cap-independent translation enhancers located in the 3′ untranslated region (3′-CITEs) have been identified in many members of the families Tombusviridae and Luteoviridae. However, viral proteins that regulate 3′-CITE-mediated translation remain unreported, and the underlying mechanisms are still poorly understood. Closteroviruses are important pathogens that infect many economically significant crops, yet their translation initiation mechanisms remain largely unexplored. Areca palm velarivirus 1 (APV1), a member of the family Closteroviridae, is the causative agent of yellow leaf disease (YLD) in areca palms. Here, we demonstrate that eukaryotic initiation factor 4E (eIF4E) specifically binds to the 3′-UTR of APV1. The APV1-encoded protein P25 interacts with eIF4E, enhances its stability, alters its subcellular localization, and promotes its recruitment to APV1 virions. Notably, P25 significantly enhances cap-independent viral translation. Knockout of eIF4E in Nicotiana benthamiana or mutation of key residues in APV1-P25 required for eIF4E interaction impairs APV1 infection. We identify the 3′-UTR of APV1 as the first reported 3′-CITE in the family Closteroviridae. Our study reveals P25 as the first viral regulator of 3′-CITE-mediated translation initiation, providing new insights into the molecular mechanisms underlying viral infection. Keywords Areca palm velarivirus 1, 3′-CITE, Translation initiation, eIF4E, P25 Background In eukaryotic cells, mRNAs typically possess a 5′-cap (m7GpppN) and a 3′-poly(A)-tail, both essential for canonical translation. The eukaryotic translation initiation factor (eIF) and poly(A)-binding protein (PABP) cooperate to initiate translation. In plants, eIF4F, a heterodimer composed of eIF4E and the scaffolding protein *Correspondence: Hongxing Wang Xi Huang 1 National Key Laboratory for Tropical Crop Breeding, School of Breeding and Multiplication (Sanya Institute of Breeding and Multiplication), Hainan University, Sanya 572025, China eIF4G, forms the initiation complex (Hinnebusch and Lorsch 2012; Hinnebusch 2014). eIF4G binds both eIF4E and PABP, which interacts with the poly(A)-tail, resulting in mRNA circularization (Aitken and Lorsch 2012). eIF4G also associates with eIF3 to recruit the 40S ribosomal subunit and initiate mRNA scanning in the 5′-to-3′ direction (Jackson et al. 2010). Unlike host mRNAs, many positive-strand RNA plant viruses lack conventional 5′-caps or poly(A) tails, necessitating alternative translation strategies. These include internal ribosome entry sites (IRESs), tRNA-like structures (TLS), and 3′-cap-independent translation enhancers (3′-CITEs), which allow viral RNAs to hijack host machinery efficiently (Nicholson and White 2011; Simon © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Wan et al. Phytopathology Research (2026) 8:24 and Miller 2013). Among these, 3′-CITEs are particularly notable for their ability to recruit translation factors to the 3′-UTR, which are then translocated to the 5′ end via long-distance RNA interactions (Karetnikov et al. 2006; Miras et al. 2017a; Truniger et al. 2017). The long-distance pairing facilitates the recruitment of the 40S ribosome complex to the 5′-UTR for scanning to the start codon (Miras et al. 2017a). While structurally diverse, 3′-CITEs are functionally conserved and have been extensively characterized in Tombusviridae and Luteoviridae (Nicholson and White 2011; Miras et al. 2017a). However, 3′-CITEs have been rarely reported in other virus families. The virus-encoded proteins regulating 3′-CITE-mediated translation remain poorly understood. The family Closteroviridae consists of seven genera and 58 species according to the current ICTV (International Committee on Taxonomy of Viruses) taxonomy release. Many members of this family are known to be pathogens that afflict economically important crops such as citrus (Dawson et al. 2013), grapevine (Naidu et al. 2015), cherry (Candresse et al. 2013), pineapple (Sether and Hu 2002), and areca palm (Wang et al. 2020). Due to the lack of natural resistance, developing disease resistance through conventional breeding is a significant challenge. The application of virus-induced gene silencing (VIGS) and novel genome-editing technologies should be considered as alternatives to classical breeding and transgenic approaches for the targeted genome modification of cultivars with resistance to viruses (Folimonov et al. 2007; Dawson and Folimonova 2013; Naidu et al. 2015). Both naturally occurring recessive eIF4E and CRISPR/ Cas9-edited eIF4E have demonstrated durable resistance in many crops without reducing yield (Nieto et al. 2006; Yeam et al. 2007; Bastet et al. 2019; Ruffel et al. 2002; Kan et al. 2023). Understanding of the translation initiation mechanism of the viral protein synthesis in the infected host cell is crucial for developing strategies to effectively control viral diseases. However, the translation initiation mechanisms of Closteroviridae remain unknown. Areca palm velarivirus 1 (APV1), first discovered in yellow leaf disease (YLD) of areca palm (Yu et al. 2015; Wang et al. 2020), belongs to the Velarivirus genus of the Closterviridae family. APV1 is a major cause of YLD in areca palms, manifesting in symptoms such as chloroplast disassembly, leaf yellowing, and reduced yield (Zhang et al. 2022; Khan et al. 2023; Cao et al. 2024). The APV1 genome encodes 11 open reading frames (ORFs), of which three ORFs at the 5’ terminal (ORF1a, ORF1b, and ORF2) encode proteins for viral RNA replication, while the virion assembly and systemic movement of closteroviruses primarily rely on the quintuple gene block (ORF3 to ORF7) located downstream of the (...truncated)