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B6R is a membrane-associated glycoprotein unique to the extracellular enveloped form of mpox virus (MPXV) and is homologous to the vaccinia virus B5R protein, sharing >96% similarity. It contains an extracellular region with four tandem complement control protein (CCP)/sushi domains and a C-terminal transmembrane helix anchoring it to the viral envelope. B6R undergoes palmitoylation, aiding its trafficking to the EEV membrane where it plays essential roles in viral egress, efficient cell-to-cell spread, and evasion of the host complement cascade. B6R is highly immunogenic and serves as a primary target for neutralizing antibodies, which can protect in animal models and inhibit virus transmission. Antibodies and vaccines targeting B6R are in preclinical and research stages as potential countermeasures for mpox. The B6R gene is also used as a specific molecular diagnostic biomarker for MPXV and is included in PCR-based detection assays.
Neutralizing antibodies bind B6R to block virus spread and/or mediate immune clearance of EEV; Candidate vaccines generate anti-B6R antibodies for immune protection
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