Accumulation of defective neuraminidase (NA) genes by influenza A viruses in the presence of NA inhibitors as a marker of reduced dependence on NA
| Autor: | Larisa V. Gubareva, Frederick G. Hayden, Marina S. Nedyalkova, Robert G. Webster |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Oseltamivir
Orthomyxoviridae Molecular Sequence Data Hemagglutinin (influenza) Acids Carbocyclic Neuraminidase Drug resistance Cyclopentanes Microbial Sensitivity Tests Viral Plaque Assay Biology medicine.disease_cause Guanidines Virus Cell Line chemistry.chemical_compound Zanamivir Acetamides Drug Resistance Viral Influenza Human Influenza A virus medicine Immunology and Allergy Animals Humans Enzyme Inhibitors biology.organism_classification Virology Infectious Diseases chemistry biology.protein medicine.drug |
| Zdroj: | The Journal of infectious diseases. 185(5) |
| ISSN: | 0022-1899 |
| Popis: | With the use of neuraminidase (NA) inhibitors (BCX-1812, oseltamivir, or zanamivir), drug-resistant variants of influenza A viruses were generated that lacked characteristic markers of resistance, such as substitutions in the NA active center or in the hemagglutinin. Drug resistance was associated with the accumulation of defective (Delta) RNA segments encoding NA. This phenomenon could be explained by reduced dependence of the virus on its NA activity. Analysis of the last isolates recovered from 11 volunteers, experimentally infected with influenza virus and treated with BCX-1812, revealed that they maintained full susceptibility to the drug in the NA inhibition assay (50% inhibitory concentration, 0.35-0.5 nM). The presence of DeltaRNA segments was detected in 1 of these isolates but was not found in the isolates recovered from placebo recipients (n = 8). Because of a lack of cell culture-based assays for susceptibility testing of human influenza viruses, detection of DeltaRNA segments should be considered an additional assay for monitoring of NA inhibitor resistance. |
| Databáze: | OpenAIRE |
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