geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Profiling and characterization of influenza virus N1 strains potentially resistant to multiple neuraminidase inhibitors


, : Profiling and characterization of influenza virus N1 strains potentially resistant to multiple neuraminidase inhibitors. Journal of Virology 89(1): 287-299

Neuraminidase inhibitors (NAIs) have been widely used to control influenza virus infection, but their increased use could promote the global emergence of resistant variants. Although various mutations associated with NAI resistance have been identified, the amino acid substitutions that confer multidrug resistance with undiminished viral fitness remain poorly understood. 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. Of the 14 single and double mutant viruses recovered in the backbone of pH1N1, four variants (E119D, E119A/D/G-H274Y) exhibited reduced inhibition by all of the NAIs and two variants (E119D and E119D-H274Y) retained the overall properties of gene stability, replicative efficiency, pathogenicity, and transmissibility in vitro and in vivo. Of the nine recombinant H5N1 viruses, four variants (E119D, E119A/D/G-H274Y) also showed reduced inhibition by all of the NAIs, though their overall viral fitness was impaired in vitro and/or in vivo. Thus, single mutations or certain combination of the established mutations could confer potential multidrug resistance on pH1N1 or HPAI H5N1 viruses. Our findings emphasize the urgency of developing alternative drugs against influenza virus infection. There has been a widespread emergence of influenza virus strains with reduced susceptibility to neuraminidase inhibitors (NAIs). We screened multidrug-resistant viruses by studying the viral fitness of neuraminidase mutants in vitro and in vivo. We found that recombinant E119D and E119A/D/G/-H274Y mutant viruses demonstrated reduced inhibition by all of the NAIs tested in both the backbone of the 2009 H1N1 pandemic (pH1N1) and highly pathogenic avian influenza H5N1 viruses. Furthermore, E119D and E119D-H274Y mutants in the pH1N1 background maintained overall fitness properties in vitro and in vivo. Our study highlights the importance of vigilance and continued surveillance of potential NAI multidrug-resistant influenza virus variants, as well as the development of alternative therapeutics.

US$19.90

PMID: 25320319

DOI: 10.1128/JVI.02485-14


Other references

Szapary-Winckemans, D.; Brunfaut, M.; Errera, M., 1968: Short term kinetics of RNA labelling in HeLa cells. European Journal of Biochemistry 4(4): 423-430

Will, U., 1988: Organization and projections of the area octavolateralis in amphibians. Unknown

Michalik, D.E.; Greene, G.; Yang, F., 2005: CSF Pleocytosis. Clinical Pediatrics 44(5): 459-462

Aveledo, H., 1963: Especie de la familia Caprimulgidae nuevo para la avifauna de Venezuela. Boletin de la Sociedad Venezolana de Ciencias Naturales, 23: 245-246

Revathy, T.; Jacob, J.John.; Jayasri, M.A.; Suthindhiran, K., 2016: Isolation and characterization of Magnetospirillum from saline lagoon. Magnetotactic bacteria (MTB) are aquatic prokaryotes that orient themselves to earth's magnetic field with the help of intracellular organelle magnetosomes. Although many species of MTB have been identified, the isolation of MTB is a challeng...

Saettone, M.F.; Et, M.T.; Giannaccini, B., 1983: Inhibition of bergaptene toxicity by UV-A filters. Synopsis It is well known that 5-methoxypsoralen (5-MOP, bergaptene) exerts several biological actions on irradiation with long wavelength (UV-A, lambda > 320 nm) UV light. The present study had the purpose of evaluating if the phototoxic activ...

Murakami, M.; Furukawa, Y.; Chiba, S., 1994: Effects of glibenclamide on negative cardiac responses to cholinergic and purinergic stimuli and cromakalim in the isolated dog heart. We investigated the effects of an ATP-sensitive K+ channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetylcholine (ACh, a muscarinic receptor agonist), ATP (a P...

RACHELE.J.R.; REED.L.J.; KIDWAI.A.R.; FERGER.M.F.; du VIGNEAUD.V., 1950: Conversion of cystathionine labeled with S35 to cystine in vivo. L-Cystathionine labeled with S35 was prepared and fed to rats for a period of 23 days. The cystine was isolated from the hair grown during this period and was found to be radioactive. The cystine was converted to 4-thiazolidinecarboxylic acid and...

Lee I.K.; Yong P.L., 1974: Some members of rhodochorton rhodophyta in korea. Korean Journal of Botany 17(1): 36-52

Gaur, A.; Chowdhury, V.K.; Yadav, R.C.; Chowdhury, J.B., 1996: High frequency plant regeneration from seedling explants of Brassica juncea (L.) Coss & Czern. Cotyledon and hypocotyl explants excised from 5-6-day-old in vitro-grown seeds of B. juncea cultivars RH30 and RH8812 were cultured on 8 MS media differing in their concentrations of growth regulators. Cultures were incubated at 25 +or- 1 degrees...