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Archives of Virology

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01.05.2008 | Original Article

Inhibition of influenza A H3N8 virus infections in mice by morpholino oligomers

verfasst von: Christopher Lupfer, David A. Stein, Dan V. Mourich, Samuel E. Tepper, Patrick L. Iversen, Manoj Pastey

Erschienen in: Archives of Virology | Ausgabe 5/2008

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Abstract

New methods to combat influenza A virus (FLUAV) in humans and animals are needed. The H3N8 subtype virus was the cause of the pandemic of 1890 and has recently undergone cross-species transmission from horses to dogs in the USA. In 2007 H3N8 spread to Australia, a continent previously devoid of equine influenza. Here, we show that antisense-peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), delivered by intranasal administration, are able to inhibit the replication of FLUAV A/Eq/Miami/1/63 (H3N8) in mice by over 95% compared to controls. Monitoring of body weight and immune cell infiltrates in the lungs of noninfected mice indicated that PPMO treatment was not toxic at a concentration shown to be effectively antiviral in vivo. In addition, we detected a naturally occurring mutation within the PPMO target site of a viral gene that may be the cause of resistance to one of the two antisense PPMO sequences tested. These data indicate that PPMOs targeting highly conserved regions of FLUAV are promising novel therapeutic candidates.

Abe T, Mizuta T, Hatta T, Miyano-Kurosaki N, Fujiwarac M, Takaia K, Shigetad S, Yokotac T, Takakua H (2001) Antisense therapy of influenza. Eur J Pharm Sci 13:61–69PubMedCrossRef

Abes S, Moulton HM, Clair P, Prevot P, Youngblood DS, Wu RP, Iversen PL, Lebleu B (2006) Vectorization of morpholino oligomers by the (R-Ahx-R)(4) peptide allows efficient splicing correction in the absence of endosomolytic agents. J Control Release 116:304–313PubMedCrossRef

Amantana A, Moulton HM, Cate ML, Reddy MT, Whitehead T, Hassinger JN, Youngblood DS, Iversen PL (2007) Pharmacokinetics, biodistribution, stability and toxicity of a cell-penetrating peptide-morpholino oligomer conjugate. Bioconjug Chem 18(4):1325–1331PubMedCrossRef

Animal Health Australia (2007) Disease strategy: equine influenza (Version 3.0). Australian Veterinary Emergency Plan (AUSVETPLAN), edn 3. Primary Industries Ministerial Council, Canberra

Arseneault D, Maghni K, Sirois P (1999) Selective inflammatory response induced by intratracheal and intravenous administration of poly-l-arginine in guinea pig lungs. Inflammation 23(3):287–304PubMed

Baz M, Abed Y, McDonald J, Boivin G (2006) Characterization of multidrug-resistant influenza A/H3N2 viruses shed during 1 year by an immunocompromised child. Clin Infect Dis 43:1555–1561PubMedCrossRef

Belser JA, Lu X, Maines TR, Smith C, Li Y, Donis RO, Katz JM, Tumpey TM (2007) Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: enhanced virulence of eurasian H7N7 viruses isolated from humans. J Virol 81:11139–11147PubMedCrossRef

Brett IC, Johansson BE (2005) Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system. Virology 339:273–280PubMedCrossRef

Burrer R, Neuman BW, Ting JP, Stein DA, Moulton HM, Iversen PL, Kuhn P, Buchmeier MJ (2007) Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. J Virol 81:5637–5648PubMedCrossRef

10.

Crawford PC, Dubovi E J, Castleman WL, Stephenson I, Gibbs EPJ, Chen L, Smith C, Hill RC, Ferro P, Pompey J, Bright RA, Medina MJ, Influenza Genomics Group, Johnson CM, Olsen CW, Cox NJ, Klimov AI, Katz JM, Donis RO (2005) Transmission of equine influenza virus to dogs. Science 310:482–485PubMedCrossRef

11.

Chutinimitkul S, Songserm T, Amonsin A, Payungporn S, Suwannakarn K, Damrongwatanapokin S, Chaisingh A, Nuansrichay B, Chieochansin T, Theamboonlers A, Poovorawan Y (2007) New strain of influenza A virus (H5N1), Thailand. Emerg Infect Dis 13(3):506–507PubMedCrossRef

12.

de Jong MD, Cam BV, Qui PT, Hien VM, Thanh TT, Hue NB, Beld M, Phuong LT, Khanh TH, Chau NVV, Hien TT, Ha DQ, Farrar J (2005) Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 352:686–691PubMedCrossRef

13.

de Jong MD, Thanh TT, Khanh TH, Hien VM, Smith GJD, Chau NV, Cam BV, Qui PT, Ha DQ, Guan Y, Peiris JSM, Hien TT, Farrar J (2005) Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 353(25):2667–2672PubMedCrossRef

14.

Deas TS, Binduga-Gajewska I, Tilgner M, Ren P, Stein DA, Moulton HM, Iversen PL, Kauffman EB, Kramer LD, Shi PY (2005) Inhibition of flavivirus infections by antisense oligomers specifically suppressing viral translation and RNA replication. J Virol 79:4599–4609PubMedCrossRef

15.

Deas TS, Bennett CJ, Jones SA, Tilgner M, Ren P, Behr MJ, Stein DA, Iversen PL, Kramer LD, Bernard KA, Shi PY (2007) In vitro resistance selection and in vivo efficacy of morpholino oligomers against West Nile virus. Antimicrob Agents Chemother 51:2470–2482PubMedCrossRef

16.

Dowdle WR (1999) Influenza A virus recycling revisited. Bull World Health Organ 77(10):820–828PubMed

17.

Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J (2004) Inhibition of influenza virus production in virus-infected mice by RNA interference. PNAS 101(32):8676–8681PubMedCrossRef

18.

Ge Q, Pastey M, Kobasa D, Puthavathana P, Lupfer C, Bestwick RK, Iversen PL, Chen J, Stein DA (2006) Inhibition of multiple subtypes of influenza A virus in cell cultures with morpholino oligomers. Antimicrob Agents Chemother 50(11):3724–3733PubMedCrossRef

19.

Govorkova EA, Leneva IA, Goloubeva OG, Bush K, Webster RG (2001) Comparison of efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother 45(10):2723–2732PubMedCrossRef

20.

Hayden FG, Pavia AT (2006) Antiviral management of seasonal and pandemic influenza. J Infect Dis194:S119–S126

21.

Holden KL, Stein DA, Pierson TC, Ahmed AA, Clyde K, Iversen PL, Harris E (2006) Inhibition of dengue virus translation and RNA synthesis by a morpholino oligomer targeted to the top of the terminal 3′ stem-loop structure. Virology 344(2):439–452PubMedCrossRef

22.

Hudziak RM, Barofsky E, Barofsky DF, Weller DL, Huang SB, Weller DD (1996) Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation. Antisense Nucleic Acid Drug Dev 6:267–272PubMed

23.

Ilyushina NA, Bovin NV, Webster RG, Govorkova EA (2006) Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70(3):121–131PubMedCrossRef

24.

Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG (2006) Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis 193:760–764PubMedCrossRef

25.

Johansson BE, Brett IC (2007) Changing perspective on immunization against influenza. Vaccine 25:3062–3065PubMedCrossRef

26.

Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, Osterhaus A (2004) Avian H5N1 influenza in cats. Science 306:241PubMedCrossRef

27.

Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KHL, Pham ND, Ngyen HH, Yamada S, Muramoto THY, Takada A, Goto H, Suzuki T, Suzuki Y, Kawaoka Y (2005) Isolation of drug-resistant H5N1 virus. Nature 437:1108PubMedCrossRef

28.

Martella V, Elia G, Decaro N, Trani LD, Lorusso E, Campolo M, Desario C, Parisi A, Cavaliere N, Buonavoglia C (2007) An outbreak of equine influenza virus in vaccinated horses in Italy is due to an H3N8 strain closely related to recent North American representatives of the Florida sub-lineage. Vet Microbiol 121:56–63PubMedCrossRef

29.

McCullers JA (2006) The clinical need for new antiviral drugs directed against influenza virus. J Infect Dis193:751–753

30.

Moulton HM, Nelson MH, Hatlevig SA, Reddy MT, Iversen PL (2004) Cellular uptake of antisense morpholino oligomers conjugated to arginine-rich peptides. Bioconjug Chem 15:290–299PubMedCrossRef

31.

National Center for Biotechnology Information. Influenza Virus Resource (2004) (cited Oct 16 2007). Available from http://www.ncbi.nlm.nih.gov/genomes/FLU/

32.

Nelson MH, Stein DA, Kroeker AD, Hatlevig SA, Iversen PL, Moulton HM (2005) Arginine-rich peptide conjugation to morpholino oligomers: effects on antisense activity and specificity. Bioconjug Chem 16:959–966PubMedCrossRef

33.

Neuman BW, Stein DA, Kroeker AD, Churchill MJ, Kim AM, Kuhn P, Dawson P, Moulton HM, Bestwick RK, Iversen PL, Buchmeier MJ (2005) Inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers. J Virol 79(15):9665–9676PubMedCrossRef

34.

Nicholls JM, Chan MCW, Chan WY, Wong HK, Cheung CY, Kwong DLW, Wong MP, Chui WH, Poon LLM, Tsao SW, Guan Y, Peiris JSM (2007) Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 13(2):147–149PubMedCrossRef

35.

Rameix-Welti MA, Agou F, Buchy P, Mardy S, Aubin JT, Veron M, van der Werf S, Naffakh N (2006) Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to Oseltamivir. Antimicrob Agents Chemother 50(11):3809–3815PubMedCrossRef

36.

Maas R, Tacken M, Ruuls L, Koch G, van Rooij E, Stockhofe-Zurwieden N (2007) Avian influenza (H5N1) susceptibility and receptors in dogs. Emerg Infect Dis 13(8):1219–1221PubMed

37.

Saito R, Li D, Suzuki Y, Sato I, Masaki H, Nishimura H, Kawashima T, Shirahige Y, Shimomura C, Asoh N, Degawa S, Ishikawa H, Sato M, Shobugawa Y, Suzuki H (2007) High prevalence of Amantadine-resistance influenza A (H3N2) in six prefectures, Japan, in the 2005–2006 season. J Med Virol 79:1569–1576PubMedCrossRef

38.

Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y (2006) Influenza virus receptors in the human airway. Nature 440:435–436PubMedCrossRef

39.

Sidwell RW, Smee DF, Huffman JH, Barnard DL, Bailey KW, Morrey JD, Babu YS (2001) In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RWJ-270201. Antimicrob Agents Chemother 45(3):749–757PubMedCrossRef

40.

Sidwell RW, Barnard DL, Day CW, Smee DF, Bailey KW, Wong MH, Morrey JD, Furuta Y (2007) Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother 51(3):845–851PubMedCrossRef

41.

Stein D, Foster E, Huang SB, Weller D, Summerton J (1997) A specificity comparison of four antisense types: morpholino, 2′-O-methyl RNA, DNA, and phosphorothioate DNA. Antisense Nucleic Acid Drug Dev 7:151–157PubMed

42.

Summerton J, Weller D (1997) Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev 7:187–195PubMed

43.

Tompkins SM, Lo CY, Tumpey TM, Epstein SL (2004) Protection against lethal influenza virus challenge by RNA interference in vivo. PNAS 101(23):8682–8686PubMedCrossRef

44.

Vagnozzi A, Stein DA, Iversen PL, Rieder E (2007) Inhibition of foot-and-mouth disease virus in cell cultures with antisense morpholino oligomers. J Virol 81(21):11669–11680PubMedCrossRef

45.

van den Born E, Stein DA, Iversen PL, Snijder EJ (2005) Antiviral activity of morpholino oligomers designed to block various aspects of equine arteritis virus amplification in cell culture. J Gen Virol 86(Pt 11):3081–3090PubMedCrossRef

46.

van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME, Kuiken T (2006) H5N1 virus attachment to lower respiratory tract. Science 312:399PubMedCrossRef

47.

Yoon KJ, Christopher VL, Schwartz KJ, Harmon KM, Kim WI, Janke BH, Strohbehn J, Butts D, Troutman J (2005) Influenza virus infection in racing Greyhounds. Emerg Infect Dis 11(12):1974–1976PubMed

48.

Yuan J, Stein DA, Lim T, Qiu D, Coughlin S, Liu Z, Wang Y, Blouch R, Moulton HM, Iversen PL, Yang D (2006) Inhibition of coxsackievirus B3 in cell cultures and in mice by peptide-conjugated morpholino oligomers targeting the internal ribosome entry site. J Virol 80:11510–11519PubMedCrossRef

49.

Zhang YJ, Stein DA, Fan SM, Wang KY, Kroeker AD, Meng XJ, Iversen PL, Matson DO (2006) Suppression of porcine reproductive and respiratory syndrome virus replication by morpholino antisene oligomers. Vet Micro 117:117–129CrossRef

Titel: Inhibition of influenza A H3N8 virus infections in mice by morpholino oligomers
verfasst von: Christopher Lupfer
David A. Stein
Dan V. Mourich
Samuel E. Tepper
Patrick L. Iversen
Manoj Pastey
Publikationsdatum: 01.05.2008
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 5/2008
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-008-0067-0

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