Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility

Nature Communications

Volumn 4, Issue , 2013, Pages

  Hai, Rong ^a   Schmolke, Mirco ^a   Leyva Grado, Victor H ^a   Thangavel, Rajagowthamee R ^a   Margine, Irina ^a   Jaffe, Eric L ^a   Krammer, Florian ^a   Solórzano, Alicia ^b   García Sastre, Adolfo ^a   Palese, Peter ^a   Bouvier, Nicole M ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b PUBLIC HEALTH RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OSELTAMIVIR; PERAMIVIR; ZANAMIVIR;

AMINO ACID; DISEASE CONTROL; DRUG RESISTANCE; ENZYME ACTIVITY; HUMAN GEOGRAPHY; IMMUNITY; INFECTIOUS DISEASE; VIRAL DISEASE; VIRULENCE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME SUBSTRATE COMPLEX; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; INFLUENZA A (H3N2); INFLUENZA VIRUS A H7N9; MOUSE; NONHUMAN; PATHOGENICITY; RECEPTOR BINDING; VIRUS REPLICATION; VIRUS TRANSMISSION; VIRUS VIRULENCE;

AVES; CAVIA; INFLUENZA A VIRUS; MUS;

AMINO ACID SUBSTITUTION; ANIMALS; ANTIVIRAL AGENTS; DRUG RESISTANCE, VIRAL; ENZYME INHIBITORS; FEMALE; HUMANS; INFLUENZA A VIRUS, H7N9 SUBTYPE; INFLUENZA, HUMAN; MICE; MICE, INBRED BALB C; NEURAMINIDASE; OSELTAMIVIR; VIRAL PROTEINS; VIRULENCE; VIRUS REPLICATION;

EID: 84890725745     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3854     Document Type: Article

References (60)

1. De J. M. D. et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med. 353, 2667-2672 (2005).
2. European Centre for Disease Prevention and Control (ECDC). ECDC/WHO frequently asked questions for Oseltamivir Resistance http://ecdc.europa.eu/en/ healthtopics/seasonal-influenza/antivirals/pages/influenza-antiviral-resistance- oseltamivir.aspx (2008).
3. Le, Q. M. et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 437, 1108 (2005). (Pubitemid 41509341)
4. World Health Organization (WHO). Overview of the emergence and characteristics of the avian influenza A(H7N9) virus http://www.who.int/ influenza/human-animal-interface/influenza-h7n9/WHO-H7N9-review-31May13.pdf (2013).
5. World Health Organization (WHO). Influenza at the human-animal interface: Summary and assessment as of 4 June 2013 http://www.who.int/influenza/human- animal-interface/Influenza-Summary-IRA-HA-;interface-04Jun 13.pdf; (2013).
6. Borse, R. H. et al. Effects of vaccine program against pandemic influenza A(H1N1) virus, United States, 2009-2010. Emerg. Infect. Dis. 19, 439-448 (2013).
7. Hsu, J. et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann. Intern. Med. 156, 512-524 (2012).
8. De Vries, E. et al. Influenza A virus entry into cells lacking sialylated N-glycans. Proc. Natl Acad. Sci. USA 109, 7457-7462 (2012).
9. Varghese, J. N., Epa, V. C. & Colman, P. M. Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci. 4, 1081-1087 (1995).
10. McKimm-Breschkin, J. L. Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance. Influenza Other Respir Viruses 7(Suppl 1): 25-36 (2013).
11. Gao, R. et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med. 368, 1888-1897 (2013).
12. Hu, Y. et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet 381, 2273-2279 (2013).
13. Bloom, J. D., Gong, L. I. & Baltimore, D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science 328, 1272-1275 (2010).
14. Bouvier, N. M., Rahmat, S. & Pica, N. Enhanced mammalian transmissibility of seasonal influenza A/H1N1 viruses encoding an oseltamivir-resistant neuraminidase. J. Virol. 86, 7268-7279 (2012).
15. Seibert, C. W., Rahmat, S., Krammer, F., Palese, P. & Bouvier, N. M. Efficient transmission of pandemic H1N1 influenza viruses with high-level oseltamivir resistance. J. Virol. 86, 5386-5389 (2012).
16. Abed, Y., Baz, M. & Boivin, G. Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds. Antivir. Ther. 11, 971-976 (2006). (Pubitemid 44955172)
17. Gubareva, L. V., Robinson, M. J., Bethell, R. C. & Webster, R. G. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J. Virol. 71, 3385-3390 (1997). (Pubitemid 27172346)
18. McKimm-Breschkin, J. L. et al. Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2enderived inhibitors. J. Virol. 72, 2456-2462 (1998). (Pubitemid 28100807)
19. Yen, H. L. et al. Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob. Agents Chemother. 49, 4075-4084 (2005).
20. Bouvier, N. M., Lowen, A. C. & Palese, P. Oseltamivir-resistant influenza A viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol. J. Virol. 82, 10052-10058 (2008).
21. Seibert, C. W. et al. Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models. J. Virol. 84, 11219-11226 (2010).
22. Carr, J. et al. Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo. Antiviral. Res. 54, 79-88 (2002). (Pubitemid 34327686)
23. Zurcher, T. et al. Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J. Antimicrob. 58, 723-732 (2006). (Pubitemid 44390944)
24. Sleeman, K. et al. R292K Substitution and Drug Susceptibility of Influenza A(H7N9) Viruses. Emerg. Infect. Dis. 19, 1521-1524 (2013).
25. Watanabe, T. et al. Characterization of H7N9 influenza A viruses isolated from humans. Nature 501, 551-555 (2013).
26. Yen, H. L. et al. Resistance to neuraminidase inhibitors conferred by an R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population. MBio 4, e00396-00313 (2013).
27. Belser, J. A. et al. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature 501, 556-559 (2013).
28. Zhang, Q. et al. H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science 341, 410-414 (2013).
29. Richard, M. et al. Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature 501, 560-563 (2013).
30. Xu, L. et al. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets. J. Infect. Dis. doi:10.1093/infdis/jit474 (2013).
31. Castrucci, M. R. & Kawaoka, Y. Biologic importance of neuraminidase stalk length in influenza A virus. J. Virol. 67, 759-764 (1993). (Pubitemid 23032053)
32. Matsuoka, Y. et al. Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J. Virol. 83, 4704-4708 (2009).
33. Yano, T., Nobusawa, E., Nagy, A., Nakajima, S. & Nakajima, K. Effects of singlepoint amino acid substitutions on the structure and function neuraminidase proteins in influenza A virus. Microbiol. Immunol. 52, 216-223 (2008).
34. Tai, C. Y. et al. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob. Agents Chemother. 42, 3234-3241 (1998). (Pubitemid 28553746)
35. Baz, M., Abed, Y., Simon, P., Hamelin, M. E. & Boivin, G. Effect of the neuraminidase mutation H274Y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza A(H1N1) viruses. J. Infect. Dis. 201, 740-745 (2010).
36. Herlocher, M. L. et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J. Infect. Dis. 190, 1627-1630 (2004). (Pubitemid 39411012)
37. Ives, J. A. et al. The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res. 55, 307-317 (2002). (Pubitemid 34718130)
38. Hamelin, M. E. et al. Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets. PLoS Pathog. 6, e1001015 (2010).
39. Kiso, M. et al. Characterization of oseltamivir-resistant 2009 H1N1 pandemic influenza A viruses. PLoS Pathog. 6, e1001079 (2010).
40. Memoli, M. J. et al. Multidrug-resistant 2009 pandemic influenza A(H1N1) viruses maintain fitness and transmissibility in ferrets. J. Infect. Dis. 203, 348-357 (2011).
41. Rayner, C. R. et al. Pharmacokinetic-pharmacodynamic determinants of oseltamivir efficacy using data from phase 2 inoculation studies. Antimicrob. Agents Chemother. 57, 3478-3487 (2013).
42. Wattanagoon, Y. et al. Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrob. Agents Chemother. 53, 945-952 (2009).
43. Abdel-Ghafar, A. N. et al. Update on avian influenza A (H5N1) virus infection in humans. N. Engl. J. Med. 358, 261-273 (2008).
44. Centers for Disease Control and Prevention (CDC). Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9) http://www.cdc.gov/flu/avianflu/h7n9-antiviraltreatment. htm (2013).
45. Cass, L. M., Efthymiopoulos, C. & Bye, A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin. Pharmacokinet. 36(Suppl 1): 1-11 (1999). (Pubitemid 29322452)
46. Nicholson, K. G. et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 355, 1845-1850 (2000). (Pubitemid 30311875)
47. Treanor, J. J. et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA 283, 1016-1024 (2000). (Pubitemid 30112215)
48. South East Asia Infectious Disease Clinical Research Network. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ 346, f3039 (2013).
49. Zhu, H. et al. Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs. Science 341, 183-186 (2013).
50. Ramos, I. et al. Effects of receptor binding specificity of avian influenza virus on the human innate immune response. J. Virol. 85, 4421-4431 (2011).
51. Quinlivan, M. et al. Attenuation of equine influenza viruses through truncations of the NS1 protein. J. Virol. 79, 8431-8439 (2005). (Pubitemid 40853545)
52. Fodor, E. et al. Rescue of influenza A virus from recombinant DNA. J. Virol. 73, 9679-9682 (1999). (Pubitemid 29487131)
53. Neumann, G. et al. Generation of influenza A viruses entirely from cloned cDNAs. Proc. Natl Acad. Sci. USA 96, 9345-9350 (1999). (Pubitemid 29374757)
54. Gaush, C. R. & Smith, T. F. Replication and plaque assay of influenza virus in an established line of canine kidney cells. Appl. Microbiol. 16, 588-594 (1968).
55. Hurt, A. Fluorometric neuraminidase inhibition assay: Standard operating procedure WHO-025 (WHO Collaborating Centre for Reference & Research on Influenza, Australia, http://www.nisn.org/documents/A.Hurt-Protocol-for-NA- fluorescence.pdf, 2007).
56. Panel on Euthanasia. AVMA Guidelines for the Euthanasia of Animals 2013 (Schaumburg, IL: American Veterinary Medical Association, 2013).
57. Reed, L. J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Hyg. 27, 493-497 (1938).
58. Thakur, A. K. & Fezio, W. L. A computer program for estimating LD50 and its confidence limits using modified Behrens-Reed-Muench cumulant method. Drug Chem. Toxicol. 4, 297-305 (1981). (Pubitemid 12133775)
59. Pica, N., Chou, Y. Y., Bouvier, N. M. & Palese, P. Transmission of influenza B viruses in the guinea pig. J. Virol. 86, 4279-4287 (2012).
60. Frey, A., Di Canzio, J. & Zurakowski, D. A statistically defined endpoint titer determination method for immunoassays. J. Immunol. Methods 221, 35-41 (1998). (Pubitemid 29017921)