Myxoma virus encodes an alpha 2,3-sialyltransferase that enhances virulence

A 4.7-kb region of DNA sequence contained at the right end of the myxoma vi rus 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 homolo gs 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 th e 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 fa mily located between genes MA51 and MA52. Detergent lysates prepared from m yxoma virus-infected cell cultures contained a virally encoded sialyltransf erase activity that catalyzed the transfer of sialic acid (Sia) from CMP-Si a to an asialofetuin glycoprotein acceptor. Analysis of the in vitro-sialyl ated 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 oligosacch aride of glycoprotein, Lectin binding assays demonstrated that alpha 2,3-si alyltransferase activity is expressed by several known leporipoxviruses tha t naturally infect Sylvilagus rabbits. The sialyltransferase is nonessentia l far myxoma virus replication in cell culture; however, disruption of the MST3N gene caused attenuation in vivo, The possible implications of the myx oma virus-expressed sialyltransferase in terms of the host's defenses again st infection are discussed.