Attenuated murine cytomegalovirus binds to N-acetylglucosamine, and shift to virulence may involve recognition of sialic acids.
Treatment of cells with lectins specific for N-acetylglucosamine (GlcNAc) blocked infection by mouse cytomegalovirus (MCMV), and GlcNAc pretreatment of the lectin blocked this effect. MCMV failed to infect N-acetylglucosaminidase (GlcNAcase)-treated mouse embryo fibroblasts (MEF). GlcNAc and GlcNAc-containing synthetic oligosaccharides directly inhibited viral infectivity. Ulex lectin inhibition of infection was shown to be due to inhibition of surface adsorption of 35S-labeled virus. Also, GlcNAcase eluted 35S-labeled virus adsorbed to MEF at 4 degrees C and inhibited plaque formation if added after adsorption at this temperature. These findings indicate that GlcNAc binding is involved in attachment rather than in some later step in infection. High-performance thin-layer chromatography overlay of [35S]MCMV indicated that it binds to a GlcNAc-containing asialoglycolipid. Analogous experiments indicated that MCMV made virulent by in vivo salivary gland passage binds to sialic acids in addition to GlcNAc. Treatment of MEF with sialic acid-binding lectins blocked infectivity. Incubation of virus with sialic acids also prevented infection. N-acetylneuraminic acid was 10(3)-fold more potent than N-glycolylneuraminic acid. Sialidase-treated target cells were not efficiently infected by the virus. Thus, MCMV binds to GlcNAc on the cell surface, and the shift to virulence (by in vivo salivary gland passage) correlates with viral recognition of sialic acids.
Ravindranath
R M
RM
Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine 90024-1769.
Graves
M C
MC
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism* / Q000472:pathogenicity; D006017:Glycolipids / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D051379:Mice; D011991:Receptors, Virus / Q000378:metabolism*; D012469:Salivary Glands / Q000382:microbiology; D012794:Sialic Acids / Q000378:metabolism*; D010948:Viral Plaque Assay
D006017:Glycolipids; D037102:Lectins; D011991:Receptors, Virus; D012794:Sialic Acids; D000117:Acetylglucosamine