Effects of hexose starvation and the role of sialic acid in influenza virus release

• Published in: Virology (New York, N.Y.) Vol. 125; no. 2; p. 324
• Main Authors: Griffin, J A, Basak, S, Compans, R W
• Format: Journal Article
• Language: English
• Published: United States 01-01-1983
• Subjects: Animals; Cattle; Cricetinae; Cytochalasin B - analogs & derivatives; Cytochalasin B - pharmacology; Cytochalasin D; Cytochalasins - pharmacology; Dogs; Glucose - deficiency; Glycoproteins - metabolism; Hexoses - metabolism; Neuraminidase - metabolism; Orthomyxoviridae - metabolism; Sialic Acids - metabolism; Time Factors
• ISSN: 0042-6822
• DOI: 10.1016/0042-6822(83)90205-2

We previously reported that growth of influenza virus in the presence of cytochalasin B (CB), a drug that disrupts microfilaments and blocks hexose transport, yields particles with glycoproteins that are heterogeneous and unlabeled by [3H]glucosamine. When the virus was grown in glucose-free medium, we observed reduced virus titers similar to those produced by CB. In contrast, treatment of cells with cytochalasin D (CD) and dihydrocytochalasin B (H2CB), drugs which are known to inhibit microfilament function without affecting hexose transport, did not cause a reduction in virus titers or a change in the electrophoretic mobility of viral glycoproteins. Partial inhibition of glycosylation of viral glycoproteins resulting from either CB-induced inhibition of hexose transport or from glucose starvation resulted in the formation of aggregates of virions on cell surfaces. These aggregates can be dissociated by exogenous neuraminidase. Under these conditions the virions contained a functional hemagglutinin glycoprotein (HA) but an inactive neuraminidase glycoprotein (NA) which was not able to cleave sialic acid, the HA receptor, from viral glycoproteins, or from cellular glycoproteins and glycolipids. Neuraminidase treatment of membrane fractions of CB-treated cells did not cause a shift in the electrophoretic mobility of HA or in the gel elution profile of HA glycopeptides obtained after extensive pronase digestion from HA synthesized in glucose-free medium. These findings suggest that sialic acid is not present on labeled glycoproteins in either of these preparations. We obtained evidence that the sialic acid to which HA binds when NA is inactive is on glycoproteins and glycolipids of cellular origin. Our results support the idea that even when NA is functional, sialylated cellular components impede influenza virus release.