Puumala virus Gn-Gc envelope glycoprotein complex (PUUV Gn-Gc)

The Puumala virus Gn-Gc envelope glycoprotein complex is a critical structural component of the Puumala orthohantavirus, which is the primary cause of nephropathia epidemica, a form of hemorrhagic fever with renal syndrome (HFRS) endemic to Europe and Russia (Wikipedia, 2024; NIH, 2021). This complex, composed of the Gn and Gc subunits, forms tetrameric spikes on the viral surface that are essential for host cell attachment and subsequent membrane fusion (MDPI, 2022; Cell Reports, 2016). The Gc subunit is characterized as a class II fusion protein, while the Gn subunit is thought to mediate receptor binding and protect the fusion loop of Gc in the prefusion state (eLife, 2020; Science Translational Medicine, 2022). As the primary target for neutralizing antibodies, the Gn-Gc complex is a focal point for the development of vaccines and therapeutic monoclonal antibodies (NIH, 2022). Experimental antibodies like ADI-42898 and P-4G2 work by binding to conserved or quaternary epitopes on the complex, thereby preventing the conformational changes necessary for viral entry (Science Translational Medicine, 2022; eLife, 2020). Despite its importance, the high genetic variability of the Gn subunit presents a significant challenge for the development of broad-spectrum therapeutics (Cell Reports, 2016).

Other names

Gn/Gc glycoprotein spikesGn-Gc hetero-octamersM polyproteinGlycoprotein G1Glycoprotein G2Puumala virus envelope glycoproteins

Neutralization of viral entry by blocking membrane fusion or receptor attachment through binding to the prefusion state of the glycoprotein complex (Science Translational Medicine, 2022; eLife, 2020).