Functional dissection of HCMV gB's autonomous fusion activity provides insights into how polymorphisms in clinical isolates confer distinct characteristics.

Polymorphisms in HCMV gB significantly alter its autonomous fusion activity, with some variants showing enhanced or abolished fusogenicity across five major genotypes.

• Why it matters: Understanding how gB polymorphisms influence fusion is crucial because it impacts viral infectivity, pathogenicity, and vaccine design, yet the mechanisms behind these effects remain unclear.
• What they did: Using a dual split protein fusion assay, the study examined five gB genotypes, identified key substitutions affecting fusion, and mapped these onto gB structural models through mutagenesis and structural analysis.
• The result: Findings reveal that specific polymorphisms can destabilize or inhibit gB conformations, enabling the identification of functionally relevant variants that could inform diagnostics and improve vaccine strategies against HCMV.