A release-competent influenza A virus mutant lacking the coding capacity for the neuraminidase active site
| Autor: | Novikov Dv, Larisa V. Gubareva, Frederick G. Hayden, Marina S. Nedyalkova, Erich Hoffmann, K. Gopal Murti |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
viruses
Molecular Sequence Data Mutant Acids Carbocyclic Neuraminidase Hemagglutinin Glycoproteins Influenza Virus Cyclopentanes Virus Replication medicine.disease_cause Guanidines Virus Cell Line Dogs Virology Influenza A virus medicine Animals Humans Receptor Gene Recombination Genetic chemistry.chemical_classification Binding Sites Base Sequence biology Active site Oligosaccharide Molecular biology N-Acetylneuraminic Acid chemistry Mutagenesis DNA Viral biology.protein |
| Zdroj: | Journal of General Virology. 83:2683-2692 |
| ISSN: | 1465-2099 0022-1317 |
| Popis: | Both influenza A virus surface glycoproteins, the haemagglutinin (HA) and neuraminidase (NA), interact with neuraminic acid-containing receptors. The influenza virus A/Charlottesville/31/95 (H1N1) has shown a substantially reduced sensitivity to NA inhibitor compared with the A/WSN/33 (H1N1) isolate by plaque-reduction assays in Madin–Darby canine kidney (MDCK) cells. However, there was no difference in drug sensitivity in an NA inhibition assay. The replacement of the HA gene of A/WSN/33 with the HA gene of A/Charlottesville/31/95 led to a drastic reduction in sensitivity of A/WSN/33 to NA inhibitor in MDCK cells. Passage of A/Charlottesville/31/95 in cell culture in the presence of an NA inhibitor resulted in the emergence of mutant viruses (delNA) whose genomes lacked the coding capacity for the NA active site. The delNA mutants were plaque-to-plaque purified and further characterized. The delNA-31 mutant produced appreciable yields (∼106 p.f.u./ml) in MDCK cell culture supernatants in the absence of viral or bacterial NA activity. Sequence analysis of the delNA mutant genome revealed no compensatory substitutions in the HA or other genes compared with the wild-type. Our data indicate that sialylation of the oligosaccharide chains in the vicinity of the HA receptor-binding site of A/Charlottesville/31/95 virus reduces the HA binding efficiency and thus serves as a compensatory mechanism for the loss of NA activity. Hyperglycosylation of HA is common in influenza A viruses circulating in humans and has the potential to reduce virus sensitivity to NA inhibitors. |
| Databáze: | OpenAIRE |
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