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The Vaccinia virus A33 protein (A33) is a highly conserved, 23-28 kDa type II integral membrane glycoprotein that is a critical component of the extracellular enveloped virus (EEV) outer membrane (UniProt, PubMed). It plays a vital role in the viral life cycle by facilitating efficient cell-to-cell spread and the egress of progeny virions from infected cells (NIH). A33 is essential for the formation of actin tails, which propel virions toward adjacent cells, and it also mediates the repulsion of superinfecting EEV to ensure rapid dissemination across the host tissue (PubMed). Structurally, the protein contains a C-type lectin-like domain and exists as a disulfide-bonded homodimer on the surface of both virions and infected cells (Journal of Virology). Due to its accessibility on the EEV surface and its role in pathogenesis, A33 is a primary target for the development of subunit vaccines and therapeutic monoclonal antibodies against orthopoxviruses, including smallpox and mpox (NIH). Neutralizing antibodies directed against A33 can inhibit the spread of infection by blocking EEV-mediated transmission, making it a key focus for medical countermeasures (PubMed).
Neutralization of extracellular enveloped virus (EEV) and inhibition of cell-to-cell spread by blocking actin tail formation and viral egress.
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