Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

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Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses.

Vyšlo v časopise: Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses. PLoS Pathog 6(8): e32767. doi:10.1371/journal.ppat.1001079
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001079

Souhrn

Zdroje

1. DawoodFS

JainS

FinelliL

ShawMW

LindstromS

2009 Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360 2605 2615

2. ItohY

ShinyaK

KisoM

WatanabeT

SakodaY

2009 In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460 1021 1025

3. MunsterVJ

de WitE

van den BrandJM

HerfstS

SchrauwenEJ

2009 Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325 481 483

4. MainesTR

JayaramanA

BelserJA

WadfordDA

PappasC

2009 Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 325 484 487

5. JainS

KamimotoL

BramleyAM

SchmitzAM

BenoitSR

2009 Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 361 1935 1944

6. Centers for Disease Control and Prevention 2009 Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep 58 433 435

7. GubarevaLV

KaiserL

HaydenFG

2000 Influenza virus neuraminidase inhibitors. Lancet 355 827 835

8. KisoM

MitamuraK

Sakai-TagawaY

ShiraishiK

KawakamiC

2004 Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 364 759 765

9. ZambonM

HaydenFG

2001 Position statement: global neuraminidase inhibitor susceptibility network. Antiviral Res 49 147 156

10. WardP

SmallI

SmithJ

SuterP

DutkowskiR

2005 Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 55 Suppl 1 i5 i21

11. LeQM

KisoM

SomeyaK

SakaiYT

NguyenTH

2005 Avian flu: isolation of drug-resistant H5N1 virus. Nature 437 1108

12. Centers for Disease Control and Prevention 2009 Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients - Seattle, Washington, 2009. MMWR Morb Mortal Wkly Rep 58 893 896

13. LeungTW

TaiAL

ChengPK

KongMS

LimW

2009 Detection of an oseltamivir-resistant pandemic influenza A/H1N1 virus in Hong Kong. J Clin Virol 46 298 299

14. LeQM

WertheimHF

TranND

van DoornHR

NguyenTH

2010 A community cluster of oseltamivir-resistant cases of 2009 H1N1 influenza. N Engl J Med 362 86 87

15. YamashitaM

TomozawaT

KakutaM

TokumitsuA

NasuH

2009 CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother 53 186 192

16. NeumannG

NodaT

KawaokaY

2009 Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459 931 939

17. IsonMG

MishinVP

BracialeTJ

HaydenFG

GubarevaLV

2006 Comparative activities of oseltamivir and A-322278 in immunocompetent and immunocompromised murine models of influenza virus infection. J Infect Dis 193 765 772

18. IlyushinaNA

BovinNV

WebsterRG

GovorkovaEA

2006 Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70 121 131

19. NguyenJT

HoopesJD

LeMH

SmeeDF

PatickAK

Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS One 5 e9332

20. IlyushinaNA

HayA

YilmazN

BoonAC

WebsterRG

2008 Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 52 3889 3897

21. GovorkovaEA

FangHB

TanM

WebsterRG

2004 Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob Agents Chemother 48 4855 4863

22. MorrisonD

RoyS

RaynerC

AmerA

HowardD

2007 A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination. PLoS ONE 2 e1305

23. HaugeSH

DudmanS

BorgenK

LackenbyA

HungnesO

2009 Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08. Emerg Infect Dis 15 155 162

24. NicollA

CiancioB

KramarzP

2008 Observed oseltamivir resistance in seasonal influenza viruses in Europe interpretation and potential implications. Euro Surveill 13

25. LackenbyA

ThompsonCI

DemocratisJ

2008 The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis 21 626 638

26. HondaT

KuboS

MasudaT

AraiM

KobayashiY

2009 Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en. Bioorg Med Chem Lett 19 2938 2940

27. GubarevaLV

WebsterRG

HaydenFG

2001 Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother 45 3403 3408

28. HatakeyamaS

SugayaN

ItoM

YamazakiM

IchikawaM

2007 Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Jama 297 1435 1442