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The Orthopoxvirus A33R protein is a 23-28 kDa type II membrane glycoprotein that is highly conserved across the Orthopoxvirus genus, including Variola, Vaccinia, and Mpox viruses [1][2]. It is specifically localized to the envelope of the extracellular enveloped virus (EEV) and is also expressed on the surface of infected host cells [2][3]. A33R is essential for the efficient cell-to-cell spread of the virus, as it facilitates the formation of actin tails and the release of EEV from the cell surface [3][4]. While the intracellular mature virus (IMV) is responsible for host-to-host transmission, the EEV form is critical for systemic dissemination within the infected host [1][5]. Due to its accessibility on the EEV surface and its role in pathogenesis, A33R is a major target for the protective immune response and is a key component in modern subunit and DNA vaccine candidates [4][6]. Monoclonal antibodies targeting A33R have demonstrated the ability to neutralize EEV and protect against lethal orthopoxvirus challenges in animal models [5][7]. Sources: [1] UniProt (P16718); [2] Galmiche et al. (1999) J. Virol.; [3] Roper et al. (1996) J. Virol.; [4] Fang et al. (2006) Virology; [5] Lustig et al. (2005) J. Virol.; [6] Matho et al. (2014) J. Biol. Chem.; [7] Benhnia et al. (2009) J. Virol.
Inhibition of extracellular enveloped virus (EEV) formation and disruption of actin-mediated cell-to-cell viral spread through antibody-mediated neutralization or immune clearance.
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