Varicella-zoster virus glycoprotein oligosaccharides are phosphorylated during posttranslational maturation.
Varicella-zoster virus (VZV)-infected human embryonic lung fibroblasts (HELF) do not release infectious virions into their growth medium. Extracellular virions are pleomorphic, suggesting that they are partially degraded before their release from cells. To examine the intracellular pathway of viral maturation, [2-3H]mannose-labeled virus-encoded glycoproteins were isolated from VZV-infected HELF. Oligosaccharides attached to the glycoproteins were processed to complex-type units, some of which were phosphorylated. The major intracellular site of accumulation of VZV gpI was found to be perinuclear and to correspond to that of the cation-independent mannose 6-phosphate (Man 6-P) receptor. Subsets of VZV-containing cytoplasmic vacuoles were coated, Golgi-associated, or accessible to endocytic tracers. Phosphorylated monosaccharides protected HELF from the cytopathic effect of VZV in proportion to their ability to block Man 6-P receptor-mediated endocytosis. These data suggest that the unusual phosphorylated oligosaccharides mediate an interaction between VZV and Man 6-P receptors of the host cell; this interaction may be responsible for withdrawal of newly synthesized virions from the secretory pathway and for their diversion to prelysosomal structures.
Gabel
C A
CA
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Dubey
L
L
Steinberg
S P
SP
Sherman
D
D
Gershon
M D
MD
Gershon
A A
AA
D003588:Cytopathogenic Effect, Viral; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D014645:Herpesvirus 3, Human / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D009844:Oligosaccharides / Q000378:metabolism*; D010766:Phosphorylation; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D013696:Temperature; D014764:Viral Proteins / Q000378:metabolism*
D006023:Glycoproteins; D009844:Oligosaccharides; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D014764:Viral Proteins