A Monoclonal Antibody Targeting mGluR2 Inhibits H9 Subtype Influenza A Virus Infection In Vitro

Metabotropic glutamate receptor 2 (mGluR2) is a critical endocytic receptor for influenza A virus (IAV) entry, making it an attractive target for host-directed antiviral interventions. A recombinant truncated fragment of mGluR2 was expressed and purified from HEK293F cells in the present investigation. Immunization of BALB/c mice followed by splenocyte fusion yielded three stable hybridoma clones: 1G3B2, 2D5A9, and 4E1C6. All three monoclonal antibodies (mAbs) exhibited strong binding affinity to both denatured and native forms of mGluR2 in Western blot and immunofluorescence assays. In vitro neutralization assays revealed that clone 1G3B2 reduced H9 subtype IAV titers by approximately 7.7 folds and suppressed intracellular viral antigen expression in a dose-dependent manner. Clones 2D5A9 and 4E1C6, while showing no viral blocking efficacy, are valuable as research tools for Western blot and IFA applications. Genetic sequencing of 1G3B2 resolved its heavy and light chain variable regions, identifying a unique, prolonged heavy-chain CDR3 loop (TRHPVNNWAWFAY). This work reports three mAbs against mGluR2 and 1G3B2 could serve as a candidate agent for developing host-directed anti-influenza therapeutics.