Myxoma virus encodes an α2,3-sialyltransferase that enhances virulence

A 4.7-kb region of DNA sequence contained at the right end of the myxoma virus EcoRI-G2 fragment located 24 kb from the right end of the 163-kb genome has been determined, This region of the myxoma virus genome encodes homologs of the vaccinia virus genes A51R, A52R, A55R, A56R, and BIR; the myxoma virus gene equivalents have been given the prefix M, The MA55 gene encodes a protein belonging to the kelch family of actin-binding proteins, while the MA56 gene encodes a member of the immunoglobulin superfamily related to a variety of cellular receptors and adhesion molecules, A novel myxoma virus early gene, MST3N, is a member of the eukaryotic sialyltransferase gene family located between genes MA51 and MA52. Detergent lysates prepared from myxoma virus-infected cell cultures contained a virally encoded sialyltransferase activity that catalyzed the transfer of sialic acid (Sia) from CMP-Sia to an asialofetuin glycoprotein acceptor. Analysis of the in vitro-sialylated glycoprotein acceptor by digestion with N-glycosidase F and by lectin binding suggested that the MST3N gene encodes an enzyme with Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase specificity for the N-linked oligosaccharide of glycoprotein, Lectin binding assays demonstrated that alpha 2,3-sialyltransferase activity is expressed by several known leporipoxviruses that naturally infect Sylvilagus rabbits. The sialyltransferase is nonessential far myxoma virus replication in cell culture; however, disruption of the MST3N gene caused attenuation in vivo, The possible implications of the myxoma virus-expressed sialyltransferase in terms of the host's defenses against infection are discussed.