Myxoma virus encodes an alpha2,3-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 B1R; 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 Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase specificity for the N-linked oligosaccharide of glycoprotein. Lectin binding assays demonstrated that alpha2,3-sialyltransferase activity is expressed by several known leporipoxviruses that naturally infect Sylvilagus rabbits. The sialyltransferase is nonessential for 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.
Jackson
R J
RJ
Vertebrate Biocontrol CRC, CSIRO Wildlife and Ecology, Canberra, Australia. R.Jackson@dwe.csiro.au
Hall
D F
DF
Kerr
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D018152:Leporipoxvirus / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009233:Myxoma virus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012799:Sialyltransferases / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase