Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes.
Method: (accessed 10/23/2014) were screened for the presence of known molecular markers (N2 numbering) of NAI resistance that demonstrated clinical relevance in human influenza A viruses of N1 (D198N, I222R, H274Y, N294S) or N2 (E119V, R292K, N294S) subtypes, and for NA markers reported in surveillance studies or in recombinant viruses of N1 (V116A, I117V, E119V, Q136L/K, V149A, Y155H, I222V/M/K,
Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.
PMID: 25588658
2015
Journal of clinical microbiology
Abstract: The R292K mutation was identified by direct testing in 3 of 11 respiratory specimens collected throughout the patient's illness but in none of the cultures from those specimens.
Abstract: We describe the case of an immunocompromised patient, positive for influenza A virus (H3N2), in whom the neuraminidase R292K mutation was transiently detected during oseltamivir treatment.
Profiling and characterization of influenza virus N1 strains potentially resistant to multiple neuraminidase inhibitors.
Abstract: We therefore screened a known mutation(s) that could confer multidrug resistance to the currently approved NAIs oseltamivir, zanamivir, and peramivir by assessing recombinant viruses with mutant NA-encoding genes (catalytic residues R152K and R292K, framework residues E119A/D/G, D198N, H274Y, and N294S) in the backbones of the 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza (HPAI) H5N1 viruses.
Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan.
PMID: 25124927
2015
The Journal of infectious diseases
Result: Applying the WHO Antiviral Working Group criteria, NA-R292K virus was characterized as exhibiting highly reduced inhibition by oseltamivir and peramivir and reduced inhibition by zanamivir, laninamivir, and A-315675.
Result: In all instances, substitutions occurred at the second nucleotide in the respective triplet: for R292K, AGG AAG; for E119V, GAA GTA; for I222R, ATA AGA; and for I222K, ATA AAA.
Result: In contrast, NA-R292K virus exhibited delayed growth, with infectious titers 2-3 logs lower than those of the other viruses and the highest titer 48 hours after infection.
Result: Inflammatory cell counts (Figure 3B) and total protein concentrations (Figure 3C) in nasal wash specimens
Multiple influenza A (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient.
PMID: 25246391
2014
Antimicrobial agents and chemotherapy
Abstract: In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy.
Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.
Discussion: The Discussion: The combination of favipiravir and ribavirin may synergistically restrict the spread of the R292K variant and needs to be tested in animal models.
Discussion: The compromised pathogenicity in vivo is attributed to the combined NA R292K and HA R220G mutations.
Discussion: The in vivo fitness of the R292K H7N9 variant virus should be further assessed with genetically well-characterized pairs of viruses and most desirably, with competitive fitness experiments.
Discussion: The lack of concordance on the in vivo fitness of the R292K variant is reminiscent of the literature on the fitness of the H274Y mutation in 2009 H1N1 pandemic viruses.
Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013.
Abstract: Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=18), A(H3N2) with NA E119V (n=3) or NA R292K (n=1) and B/Victoria-lineage with NA H273Y (n=2); amino acid position numbering is A subtype and B type specific.
Method: An A(H3N2) virus with a R292K NA substitution was also recovered from an oseltamivir-treated patient.
Method: The E119V and R292K substitutions were also detected in the corresponding clinical specimens.
Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.
PMID: 24951824
2014
The Journal of infectious diseases
Abstract: An NA-R292K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment.
Abstract: CONCLUSIONS: The NA inhibitor-resistant H7N9 virus with the NA-R292K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
Abstract: In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection.
Abstract: METHODS: We evaluated the transmission potential of a human influenza A H7N9 isolate with
PCR for detection of oseltamivir resistance mutation in influenza A(H7N9) virus.
Abstract: Sensitive molecular techniques are needed for rapid detection of the R292K oseltamivir-resistant mutant of influenza A(H7/N9) virus strain to monitor its transmission and guide antiviral treatment.
Introduction: Studies have shown that the NA R292K mutation can cause a high level of resistance to oseltamivir in influenza A(H7N9) virus .
Introduction: We reported emergence of an influenza virus with a mutation in the neuraminidase (NA) gene (R292K) and its association with severe clinical outcome in infected persons.
Method: Seven of 11 samples had positive results in the R292K assay: 5 samples positive in the 292K assay and 2 samples positive in both assays.
Method: The <
An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality.
PMID: 24569063
2014
The Journal of infectious diseases
Method: Because these influenza A(H7N9) isolates contained a mixed viral population, plaque purification was performed in MDCK-SIAT1 cells to separate the oseltamivir-resistant virus variant carrying R292K from the wild-type virus with R292.
Method: Sanger sequencing analyses of the plaque-purified viruses confirmed that R292K was the only amino acid difference between the NAs of wild-type and R292K virus variant.
Method: The HA of the Shanghai/1 R292K variant had a mixture of 151A/S (2013 H7 numbering) and 209G/E, while that of the Taiwan/1 R292K variant showed a D340G substitution, compared with characteristics of the respective wild-type viruses.
IV mutation literature information.
PMID: 
2015
Antiviral research
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