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A release-competent influenza A virus mutant lacking the coding capacity for the neuraminidase active site.
- Source :
-
The Journal of general virology [J Gen Virol] 2002 Nov; Vol. 83 (Pt 11), pp. 2683-2692. - Publication Year :
- 2002
-
Abstract
- 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 ( approximately 10(6) 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.
- Subjects :
- Acids, Carbocyclic
Animals
Base Sequence
Binding Sites
Cell Line
DNA, Viral
Dogs
Guanidines
Hemagglutinin Glycoproteins, Influenza Virus genetics
Humans
Influenza A virus drug effects
Influenza A virus genetics
Influenza A virus physiology
Molecular Sequence Data
Mutagenesis
N-Acetylneuraminic Acid metabolism
Neuraminidase antagonists & inhibitors
Neuraminidase genetics
Recombination, Genetic
Virus Replication
Cyclopentanes pharmacology
Hemagglutinin Glycoproteins, Influenza Virus metabolism
Influenza A virus enzymology
Neuraminidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1317
- Volume :
- 83
- Issue :
- Pt 11
- Database :
- MEDLINE
- Journal :
- The Journal of general virology
- Publication Type :
- Academic Journal
- Accession number :
- 12388803
- Full Text :
- https://doi.org/10.1099/0022-1317-83-11-2683