GTPase GBP7 promotes HSV-1 infection by interacting with and activating eEF1A1 to accelerate the protein translation process
4 affiliations
- 1Guangdong Provincial Key Laboratory of New Drug Screening, Guangdong-Hong kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
- 2Department of Pharmacy, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 3NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Department of Pharmacy, Pingshan Hospital, Southern Medical University, Shenzhen, China
- 4State Key Laboratory of Multi-organ Injury Prevention and Treatment, MOE Key Laboratory of Infectious Diseases Research in South China, MOE Innovation Center for Medical Basic Research on Inflammation and Immune Related Diseases, Southern Medical University, Guangzhou, China
Abstract
Guanylate-binding proteins (GBPs) are immune GTPases induced by interferons (IFNs) and comprise GBPs1-7. In this study, GBP7, a less studied member of the GBPs, was identified to possess Herpes simplex virus I (HSV-1) promoting effects on replication both in vitro and in vivo. Knockdown of GBP7 or loss of its GTPase activity demonstrated significant antiviral effects. Consistently, GBP7-/- mice infected with HSV-1 showed higher survival and milder symptoms. Mechanistically, we discovered GBP7 directly binds to eukaryotic translation elongation factor 1α1 (eEF1A1), which was validated through immunoprecipitation mass spectrum (IP-MS) and binding affinity assays. GBP7 utilizes its GTPase activity to assist eEF1A1 in GTP hydrolysis, activating its role in promoting protein translation, thereby increasing viral replication and infection. Moreover, through high-throughput virtual screening, S-Adenosylhomocysteine (SAH) was identified as a novel GBP7 targeting inhibitor, which demonstrated potent antiviral activity against HSV-1infection and broad-spectrum potentiality. Collectively, these findings uncover the critical role of the GBP7-eEF1A1 axis in viral infection and provide theoretical basis for host-targeted antiviral therapy. Author summary: Guanylate-binding proteins (GBPs) are recognized as integral components of the IFN-γ-induced defense system against pathogenic microbial infections, particularly human GBPs1-7. In our study, it was discovered that GBP7 was highly expressed in virus-infected cells and to a certain extent promoted the infection process which indicated a host factor facilitating viral infection and a potential antiviral drug target. Protein interaction research and enzyme activity detection demonstrated that GBP7 was highly probable to facilitate the translation elongation function of eEF1A1 by leveraging its GTPase activity. The interaction mode and key binding sites between eEF1A1 and GBP7 in this study provided insights of the protein structure of the complex. Additionally, we discovered the broad antiviral activity of the compound SAH and identified GBP7 as a novel host target for the rational design of broad-spectrum antiviral inhibitors.
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BibTeX
@article{wang2026gtpase,
title = {{GTPase GBP7 promotes HSV-1 infection by interacting with and activating eEF1A1 to accelerate the protein translation process}},
author = {Jinshen Wang and Liangbing Man and Binhao Rong and Kunyu Lu and Luping Cheng and Jianfu He and Haowei Li and Hao Su and Xinxin Lin and Ru Li and Min Zou and Chan Yang and Shuwen Liu},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014652},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014652},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - GTPase GBP7 promotes HSV-1 infection by interacting with and activating eEF1A1 to accelerate the protein translation process
AU - Jinshen Wang
AU - Liangbing Man
AU - Binhao Rong
AU - Kunyu Lu
AU - Luping Cheng
AU - Jianfu He
AU - Haowei Li
AU - Hao Su
AU - Xinxin Lin
AU - Ru Li
AU - Min Zou
AU - Chan Yang
AU - Shuwen Liu
PY - 2026
DA - 2026/10/12
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014652
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014652
AB - Guanylate-binding proteins (GBPs) are immune GTPases induced by interferons (IFNs) and comprise GBPs1-7. In this study, GBP7, a less studied member of the GBPs, was identified to possess Herpes simplex virus I (HSV-1) promoting effects on replication both in vitro and in vivo. Knockdown of GBP7 or loss of its GTPase activity demonstrated significant antiviral effects. Consistently, GBP7-/- mice infected with HSV-1 showed higher survival and milder symptoms. Mechanistically, we discovered GBP7 directly binds to eukaryotic translation elongation factor 1α1 (eEF1A1), which was validated through immunoprecipitation mass spectrum (IP-MS) and binding affinity assays. GBP7 utilizes its GTPase activity to assist eEF1A1 in GTP hydrolysis, activating its role in promoting protein translation, thereby increasing viral replication and infection. Moreover, through high-throughput virtual screening, S-Adenosylhomocysteine (SAH) was identified as a novel GBP7 targeting inhibitor, which demonstrated potent antiviral activity against HSV-1infection and broad-spectrum potentiality. Collectively, these findings uncover the critical role of the GBP7-eEF1A1 axis in viral infection and provide theoretical basis for host-targeted antiviral therapy. Author summary: Guanylate-binding proteins (GBPs) are recognized as integral components of the IFN-γ-induced defense system against pathogenic microbial infections, particularly human GBPs1-7. In our study, it was discovered that GBP7 was highly expressed in virus-infected cells and to a certain extent promoted the infection process which indicated a host factor facilitating viral infection and a potential antiviral drug target. Protein interaction research and enzyme activity detection demonstrated that GBP7 was highly probable to facilitate the translation elongation function of eEF1A1 by leveraging its GTPase activity. The interaction mode and key binding sites between eEF1A1 and GBP7 in this study provided insights of the protein structure of the complex. Additionally, we discovered the broad antiviral activity of the compound SAH and identified GBP7 as a novel host target for the rational design of broad-spectrum antiviral inhibitors.
SN - 1553-7374
ER -