Puumala virus envelope glycoprotein Gn (PUUV Gn)

Puumala virus envelope glycoprotein Gn is a primary surface protein of the Puumala orthohantavirus, the leading cause of hemorrhagic fever with renal syndrome (HFRS) and its milder variant, nephropathia epidemica, in Europe and Russia [4, 5]. Encoded by the viral M genomic segment, Gn is co-translationally cleaved and associates with the Gc glycoprotein to form heterotetrameric spikes that facilitate viral entry into host cells [11, 22]. Gn specifically mediates attachment to host receptors, such as beta-3 integrins (ITGAV/ITGB3), and coordinates virion assembly by interacting with the viral nucleocapsid protein [3, 6, 11]. Beyond structural roles, Gn is involved in immune evasion by inducing mitochondrial autophagy and degrading mitochondrial antiviral-signaling (MAVS) proteins, thereby suppressing the host's type I interferon response [6]. As the most exposed component of the viral envelope, Gn is the principal target for neutralizing antibodies and a focal point for vaccine development [14, 16]. While there are currently no FDA-approved therapeutics targeting Gn, several neutralizing monoclonal antibodies (nAbs) are in development. For example, the experimental antibody ADI-42898 targets a quaternary epitope within the Gn/Gc complex, offering broad protection across various hantavirus species by locking the spike in its pre-fusion conformation [14, 16, 17]. Therapeutic strategies focusing on Gn aim to interrupt the early stages of the viral life cycle to prevent the systemic vascular leakage and acute renal failure characteristic of hantavirus infections [5, 18].

Other names

Glycoprotein G1Hantavirus G1 proteinGn proteinPuumala orthohantavirus GnEnvelope glycoprotein G1

Neutralization of viral entry by blocking binding to host receptors (such as beta-3 integrins) and preventing the conformational changes in the Gn/Gc complex necessary for endosomal membrane fusion [14, 16].