Inhibition of cellular DNA synthesis by reovirus occurs through a receptor-linked signaling pathway that is mimicked by antiidiotypic, antireceptor antibody.
Mammalian reovirus type 3 binds to a 67-kD surface glycoprotein on the membrane of neuronal cells. This interaction initiates the infective reovirus cycle. The physiological function of this virus receptor is not known, however, initial studies illustrate a striking structural and antigenic homology to the beta adrenergic receptor family. The earliest known pathologic effect of reovirus type 3 is an inhibition of host cell DNA synthesis within 8-10 h after virus attachment. The studies reported here demonstrate that binding and aggregation of reovirus receptor molecules provides the signal for this inhibitory process. Inhibition of DNA synthesis in the neuroblastoma cell line B104.G4 was unaffected by using replication-defective virus or when lysosomal processing of normal virus was blocked. Inhibition was mimicked by an antiidiotypic, antireceptor mAb. Inhibition was not observed when monovalent mAb fragments were bound to receptors, but was reconstituted when these fragments were aggregated by the addition of anti-Ig. The signal for the inhibitory effect was generated within the first 60 min after mAb binding. These observations demonstrate that reovirus and antiidiotypic pathogenicity can result from the perturbation of membrane proteins that may perform normal physiological functions.
Gaulton
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GN
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Greene
M I
MI
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000937:Antigen-Antibody Reactions; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000096:biosynthesis*; D008247:Lysosomes / Q000187:drug effects; D012089:Mammalian orthoreovirus 3 / Q000254:growth & development / Q000472:pathogenicity*; D009447:Neuroblastoma; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology*; D012087:Reoviridae / Q000472:pathogenicity*; D012088:Reoviridae Infections / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D011991:Receptors, Virus; D004247:DNA; D000242:Cyclic AMP