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The Monkeypox virus B6R protein is a palmitoylated glycoprotein and a key structural component of the extracellular enveloped virion (EEV) form of the virus, homologous to vaccinia virus B5R with 96.53% similarity. It plays essential roles in viral dissemination by facilitating efficient infection spread, regulating the host complement system to evade immunity, enabling dissolution of the EEV outermost membrane for host cell entry, and supporting EEV wrapping and transmission. Expressed from genes in the conserved central genomic region of monkeypox virus (MPXV), an orthopoxvirus, B6R localizes to infected cell surfaces and EEV membranes via lipid modifications. In disease contexts, B6R contributes to MPXV pathogenesis, including attachment, fusion, replication, assembly, and release, making it a critical factor in mpox outbreaks. Therapeutic antibodies like hMB621, hMB668, and bispecific constructs such as A9F8-B7C9 target B6R epitopes, demonstrating potent neutralization against MPXV and related orthopoxviruses in vitro and in vivo, with protective effects in mouse models against lethal challenges. These antibodies bind broadly to B6 orthologs, inhibit EEV release, and offer promise for treating orthopoxvirus infections, including mpox, with some candidates selected for mRNA vaccines or PCR diagnostics.
Neutralization of extracellular enveloped virions (EEV), Binding to distinct epitopes on B6 to prevent viral entry and spread, Cross-neutralization of orthopoxviruses including vaccinia virus (VACV), variola virus (VARV), and cowpox virus (CPXV), Inhibition of comet-like plaque formation by EEV
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