The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence

Vaccinia virus (VV) gene A41 L encodes an acidic protein with amino acid similarity to the 35 kDa protein of VV strain Lister, a soluble protein called vCKBP that binds CC chemokines, and to a protein from orf virus, called GIF, that binds GM-CSF and IL-2. However, despite the similarity, recombinantA41 L protein was found not to bind these ligands or a variety of other chemoattractant molecules when tested using surface plasmon resonance. The A41 L gene is expressed early and late during infection and encodes a 30 kDa protein that contains both N- and O-linked carbohydrate and is secreted from the infected cell. All 16 strains of VV and 2 strains of cowpox virus that were tested express the A41 L protein, implying it has an important function for orthopoxviruses. Nonetheless, a VV strain Western Reserve deletion mutant lacking the A41 L gene (v Delta A41 L) formed normal sized plaques and replicated to the same titre as wild-type and revertant viruses. The importance of the A41 L protein in vivo was demonstrated in a mouse intradermal model in which infection with v Delta A41 L caused more severe lesions compared to wild-type and revertant viruses. Further examination in this model revealed that deletion of A41 L enhanced clearance of infectious virus, suggesting that A41 L expression reduces immunopathology. Consistent with this, histological examination of infected rabbit skin showed that the A41 L protein could reduce the infiltration of inflammatory cells into the infected area. Together, these data suggest that the A41 L protein constitutes a novel immunomodulatory protein.