Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants. Two (4%) of 54 resistant viruses were detected by NA inhibition assay among last-day isolates recovered from 54 drug recipients. They bore a substitution His274Tyr in the NA. Hemagglutinin (HA) variants detected in the placebo group differed from the egg-adapted inoculum virus by virtue of amino acid substitutions at residues 137, 225, or both. These variants had a higher affinity for Neu5Ac(alpha2-6)Gal-containing receptors, which are characteristic of human respiratory epithelium, than for Neu5Ac(alpha2-3)Gal-containing receptors, which are typical of chicken egg allantoic membrane. Although appearing to be more sensitive to oseltamivir in humans, the variants with increased affinity for Neu5Ac(alpha2-6)Gal receptors were less sensitive than the Neu5Ac(alpha2-3)Gal-binding variants in Madin-Darby canine kidney cells. Thus, HA affinity for receptors is an essential feature of influenza virus susceptibility to NA inhibitors, both in cell culture and in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1899
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
523-31
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11170976-Acetamides, pubmed-meshheading:11170976-Adolescent, pubmed-meshheading:11170976-Adult, pubmed-meshheading:11170976-Amino Acid Substitution, pubmed-meshheading:11170976-Animals, pubmed-meshheading:11170976-Antiviral Agents, pubmed-meshheading:11170976-Base Sequence, pubmed-meshheading:11170976-Cell Line, pubmed-meshheading:11170976-Dogs, pubmed-meshheading:11170976-Drug Resistance, Microbial, pubmed-meshheading:11170976-Genetic Variation, pubmed-meshheading:11170976-Hemagglutinin Glycoproteins, Influenza Virus, pubmed-meshheading:11170976-Humans, pubmed-meshheading:11170976-Influenza, Human, pubmed-meshheading:11170976-Influenza A virus, pubmed-meshheading:11170976-Microbial Sensitivity Tests, pubmed-meshheading:11170976-Molecular Sequence Data, pubmed-meshheading:11170976-Mutation, pubmed-meshheading:11170976-Neuraminidase, pubmed-meshheading:11170976-Oseltamivir, pubmed-meshheading:11170976-Receptors, Virus, pubmed-meshheading:11170976-Viral Plaque Assay
pubmed:year
2001
pubmed:articleTitle
Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir.
pubmed:affiliation
Department of Internal Medicine, Division of Epidemiology and Virology, University of Virginia, PO Box 473, Charlottesville, VA 22908, USA. lvg9b@virginia.edu
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial, Research Support, Non-U.S. Gov't