Finding the Goldilocks zone: modulating glycoprotein cleavage and fusogenicity optimizes the efficacy of a candidate Crimean-Congo hemorrhagic fever virus vaccine.

SKI-1 cleavage at the GP38-Gn boundary in CCHFV glycoprotein complex is linked to a modulated pH threshold for membrane fusion, shaping rVSV-GPC vaccine infectivity.

• Why it matters: Limited mechanistic understanding of CCHFV assembly, egress, and entry has hindered vaccine development, despite the need for countermeasures against a highly lethal tick-borne hemorrhagic disease.
• What they did: Using a highly protective recombinant vesicular stomatitis virus vaccine bearing the CCHFV glycoprotein complex (rVSV-GPC), the study mapped adaptation-associated amino acid residues and transferred a minimal set into a divergent CCHFV background.
• The result: The substitutions enhanced rVSV-GPC infectivity through multiple biochemical and cell-biological mechanisms, and SKI-1 cleavage was the first evidence shown to modulate the fusion pH threshold.

AI summary of the abstract · may contain errors · not medical advice · read the paper.