GTPase GBP7 promotes HSV-1 infection by interacting with and activating eEF1A1 to accelerate the protein translation process

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.