Vaccinia virus A33R protein (A33R)

The Vaccinia virus A33R protein is a highly conserved 23- to 28-kDa glycoprotein encoded by the A33R gene, forming a disulfide-bonded homodimer with N- and O-linked glycosylation. It is a type II transmembrane protein specifically incorporated into the viral outer envelope of extracellular enveloped virions (EEV), essential for efficient EEV formation, long-range viral spread, and cell-to-cell dissemination via actin tails. A33R provides chaperone function for A36R membrane localization and tyrosine phosphorylation, and coordinates incorporation of other proteins like B5 into EV membranes. Its ectodomain features an unusual C-type lectin-like domain (CTLD) structured as a flexible dimer similar to NK-cell receptor class CTLDs or Link modules, lacking a canonical carbohydrate-binding site but potentially binding viral or host ligands. Deletion mutants produce small plaques with comet tails, confirming its non-essential but critical role in replication. A33R is a target for neutralizing antibodies that recognize conformational epitopes.

Other names

A33 proteinOPG161

Neutralization of extracellular enveloped virus by binding conformational epitopes on A33 dimer, blocking viral spread