Target intelligence / Profile preview

Orthopoxvirus A33 protein (A33)

Target
A33
Molecular classification
Viral envelope protein, Type II transmembrane glycoprotein, C-type lectin-like domain protein
01

Overview

The Orthopoxvirus A33 protein is a 23-28 kDa type II transmembrane glycoprotein essential for the dissemination of orthopoxviruses like Variola (smallpox) and Mpox (UniProt P33835). It is specifically located on the outer membrane of the extracellular enveloped virus (EEV) and is required for the efficient wrapping of intracellular mature virus (IMV) and the subsequent formation of actin tails for cell-to-cell spread (PubMed: 11832461). Because the EEV form is crucial for systemic spread and immune evasion, A33 is a major target for protective immunity and vaccine design (PubMed: 15141014). Antibodies targeting A33 do not neutralize the IMV form but instead prevent the release and spread of EEV, providing a distinct mechanism of protection compared to other viral targets (PubMed: 17507481). It is a key component in next-generation subunit vaccines and is a target of the antibodies found in Vaccinia Immune Globulin Intravenous (VIGIV) used to treat complications from smallpox vaccination (FDA: VIGIV Label). The protein's conserved nature across the Orthopoxvirus genus makes it a versatile target for broad-spectrum poxvirus countermeasures.

Other names
A33R proteinEnvelope glycoprotein A33p35Vaccinia virus A33R proteinA33R
02

Mechanism of action

Induction of neutralizing antibodies that inhibit the formation and spread of extracellular enveloped virus (EEV) and block actin-mediated cell-to-cell transmission.

03

Biological functions

Viral egressCell-to-cell spreadExtracellular enveloped virus (EEV) formationActin tail formationViral assembly
04

Disease associations

InfectionSmallpoxMpox (Monkeypox)Vaccinia
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Safety considerations

Immunogenicity-related adverse eventsPotential for viral escape through mutations in the A33R geneRisk of adverse reactions to live-virus vaccines containing the protein
06

Interacting drugs

ACAM2000 (Vaccinia Virus Vaccine)

2 more in the full profile.

07

Biomarkers

Anti-A33 antibody titerA33-specific T-cell response

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