Structural basis of hypervariable region 1 dynamics on HCV envelope glycoproteins in immune evasion.

X-ray crystallography and nsEM show that hepatitis C virus HVR1 AS399 (residues 399–409) is highly flexible and dynamically shields epitopes even when other neutralizing antibodies are bound.

• Why it matters: HVR1 drives immune evasion, but the unresolved C-terminal segment (394–411) has limited understanding of how its conformation controls shielding and receptor recognition.
• What they did: Using nAb RM1-38 targeting C-terminal HVR1 AS399, the study combined crystal structures of RM1-38 Fab with the AS399 peptide, mutagenesis, nsEM, and competition ELISA, plus virus neutralization and receptor-binding assays.
• The result: RM1-38 recognition is strain-specific, HVR1 remains conformationally flexible with other nAbs, RM1-38 antagonizes bnAbs, and it reduces SR-BI binding while leaving CD81 binding unchanged.

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