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
Result: Screening for markers of NAI resistance reported in surveillance or experimental studies revealed 0.38% (13/3396) sequences with the I117V-NA (including 3 IAV-S from this study), 0.24% (8/3396) with the Y155H-NA, and 0.09% (3/3396) with the E119K-NA among N1; 0.24% (8/3396) sequences with the V149A-NA, 0.15% (5/3396) with the I222V-NA, and 0.06% (2/3396) with the Y155H-NA among the N2 IAV-S (Table 3).
A novel I221L substitution in neuraminidase confers high-level resistance to oseltamivir in influenza B viruses.
PMID: 24795482
2014
The Journal of infectious diseases
Discussion: As for the I223V/R and H275Y substitutions in N1, the N2-I222V substitution alone confers a slight increase in oseltamivir IC50 but acts in synergy with E119V (in N2) to yield highly reduced inhibition by oseltamivir.
Discussion: Substitutions at position I222V (N2 numbering) have also been described in patients undergoing treatment for influenza A(H3N2) virus infections.
Study of oseltamivir and zanamivir resistance-related mutations in influenza viruses isolated from wild mallards in Sweden.
Method: The literature describing NAI resistance mutations has been reviewed, whereupon nine OC (V116A, I117V, E119V, D198N, I222V, H274Y, R292K, N294S and I314V) and ten ZA (V116A, R118K, E119G/A/D, Q136K, D151E/G/N, R152K, R224K, E276D, R292K and R371K)
Susceptibility of avian influenza viruses of the N6 subtype to the neuraminidase inhibitor oseltamivir.
Result: The I222V NA mutation has been shown to confer reduced susceptibility of human influenza viruses of the N1 and N2 NA subtypes to oseltamivir in phenotypic assays.
Discussion: Among 5490 avian NA sequences from the NCBI database and from a European bird observatory, 6 of 55 influenza viruses analyzed of the N6 NA subtype (10.91%) had the NA catalytic residue change R152K, and 2 viruses (4%) had the I222V NA framework mutation.
Discussion: Our sequence analysis verified an I222V NA residue change in two virus isolates (A/Herring Gull/Delaware/660/1988 and A/Herring Gull/Delawar
The I222V neuraminidase mutation has a compensatory role in replication of an oseltamivir-resistant influenza virus A/H3N2 E119V mutant.
PMID: 21106781
2011
Journal of clinical microbiology
Abstract: Based on plaque size, yield assays, and NA activity, the impaired viral fitness of the E119V mutant was partially restored by the I222V NA mutation.
Abstract: Oseltamivir-resistant A/H3N2 influenza isolates with or without the E119V and I222V neuraminidase (NA) mutations were recovered from an immunocompromised patient.
Oseltamivir-resistant pandemic H1N1/2009 influenza virus possesses lower transmissibility and fitness in ferrets.
Introduction: These studies differed in the influenza A subtypes studied (H1N1, H3N2, or H5N1), the NA mutations involved (H275Y, R292K, E119V or I222V), the animal model used (ferret or guinea pig), and the transmission routes studied (direct contact and respiratory droplets); in these studies, the transmissibility of most of the NA inhibitor-resistant influenza viruses was to some extent less efficient.
Discussion: The only study to date that has evaluated both routes of transmission of oseltamivir-resistant virus showed that recombinant resistant H3N2 viruses with either the E119V or the E119V+I222V NA mutation were transmitted effici
Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein.
Result: In the NI assay, oseltamivir failed to effectively inhibit NA activity from each of the 2007 and 2009 isolates; however, all of these isolates were equally sensitive to zanamivir, including the 2009 isolates that
Discussion: An NA mutation (I222V) was observed in two of the zanamivir-resistant 2009 seasonal IFV strains, in addition to the well described H274Y mutation.
Discussion: Drug sensitivity analysis was not performed on these viral isolates, therefore the significance of the I222V mutation in patients is unclear.
Discussion: Previous in vitro selection studies have indicated that the I222V mutation exacerbates oseltamivir- and peramivir-resistance caused by H274Y, but has only modest affect on zanamivir sensitivity.
Oseltamivir-resistant influenza A viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol.
Abstract: Here, we demonstrate that recombinant human influenza A/H3N2 viruses without and with oseltamivir resistance mutations (in which NA carries the mutation E119V or the double mutations E119V I222V) have similar in ovo growth kinetics and infectivity in guinea pigs.
IV mutation literature information.
PMID: 
2015
Antiviral research
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