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The Vaccinia virus B5 protein (encoded by the B5R gene) is a 42-kDa type I membrane glycoprotein essential for the formation and dissemination of the extracellular enveloped virus (EEV) form of orthopoxviruses. It is located on the outer envelope of EEV and plays a critical role in wrapping mature virions (MV) to form intracellular enveloped virions (IEV), as well as in the subsequent release of EEV from the host cell. B5 is necessary for the induction of actin tails that propel the virus away from the infected cell and for the repulsion of superinfecting virions, a strategy that accelerates viral spread across cell monolayers. Structurally, B5 contains four short consensus repeats (SCRs) similar to those found in host complement control proteins, suggesting a role in immune evasion by protecting the virus from complement-mediated destruction. As a primary target for neutralizing antibodies, B5 is a key component of smallpox and mpox vaccines, such as ACAM2000 and JYNNEOS, and is a focus for the development of therapeutic monoclonal antibodies and subunit vaccines. Effective immunity against orthopoxviruses typically requires a combination of antibodies targeting both the B5 protein on EEV and surface proteins on the MV form.
Neutralization of extracellular enveloped virus (EEV) particles and inhibition of cell-to-cell spread by blocking actin tail formation and viral repulsion.
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