Disease relevance of A36R

• A characterization of vaccinia virus strain Western Reserve (WR) open reading frame (ORF) A36R is described [1].
• IMV formation by delta A36R was unaltered but EEV formation was reduced approximately fivefold compared to wild-type (WT) when measured either by density gradient analysis of isotopically labeled virions or by infectivity assays [1].

High impact information on A36R

• Here we show that phosphorylation of tyrosine 112 in the viral protein A36R by Src-family kinases is essential for the actin-based motility of vaccinia [2].
• (b) VV mutants lacking the A33R, A34R, or A36R proteins are unable to induce actin tail formation but produce CEV and extracellular-enveloped virus [3].
• Remarkably, both mutants failed to form actin tails and specialized microvilli, despite the presence of an intact A36R gene [4].
• The use of a small plaque-forming A36R gene deletion mutant to select spontaneous second-site mutants exhibiting enhanced virus release was described previously [4].
• Considerably more extracellular enveloped virus was released into the medium by the second-site mutants than by the parental A36R deletion mutant, explaining their selection in tissue culture as well as their comet-forming phenotype [5].

Biological context of A36R

• A WR deletion mutant lacking the A36R ORF (delta A36R) had a small plaque phenotype on all cell lines tested [1].
• Finally, a revertant virus in which the A36R ORF was restored showed WT plaque size, EEV formation, and virulence, demonstrating that all the phenotypic differences of delta A36R were attributable to loss of the A36R gene and not to other mutations acquired during its construction [1].
• The assay's specificity utilised unique single nucleotide polymorphisms (SNP) identified among Orthopoxvirus (OPV) orthologs of the vaccinia virus Copenhagen strain A13L and A36R genes [6].
• Serine phosphorylation and A33R-A36R protein complex formation occurred even when virus assembly was blocked at an early stage with the drug rifampin [7].
• In addition, increased expression of cellular phospholipase D, which has a similar phospholipase motif as, but little amino acid sequence identity with, F13L, induced post-Golgi vesicles that contained B5R and A36R proteins [8].

Anatomical context of A36R

• A36R was also transported to the plasma membrane, where it accumulated at the tips of cell projections [9].
• Moreover, this actin tail-independent movement was indistinguishable from that of a control virus with an unmutated A36R gene and closely resembled the movement of vesicles on microtubules [10].
• Immunofluorescence and immunoelectron microscopy indicated that in the absence of the A33R protein, the A36R protein was localized in Golgi membranes but not in IEV [7].
• Protein A36R was partially retained intracellularly, decorating both the Golgi complex and structures associated with actin fibers [9].
• In spite of their selective advantage in cultured cells, the second-site mutants were not detectably more virulent than the A36R deletion mutant when administered to mice by the intranasal route [5].

Associations of A36R with chemical compounds

• The A36R protein was also phosphorylated on tyrosine, as determined by specific binding to an anti-phosphotyrosine antibody [7].

Other interactions of A36R

• In this report we provide evidence that the A22R and A36R open reading frames also encode palmitylproteins with apparent molecular masses of 22 and 50-55 kDa, respectively [11].

References