Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Virology Journal
Published in: Virology Journal 1/2010

Open Access 01-12-2010 | Research

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

Authors: John A Lednicky, Sara B Hamilton, Richard S Tuttle, William A Sosna, Deirdre E Daniels, David E Swayne

Published in: Virology Journal | Issue 1/2010

Login to get access

Abstract

Background

There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed.

Results

Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret.

Conclusions

Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.
Appendix
Available only for authorised users
Literature
1.
2.
Maines TR, Chen L-M, Matsuoka Y, Chen H, Rowe T, Ortin J, Falcón A, Hien NT, Mai LQ, Sedyaningsih ER, Harun S, Tumpey TM, Donis RO, Cox NJ, Subbarao K, Katz JM: Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci USA 2006, 103: 12121-12126. 10.1073/pnas.0605134103PubMedPubMedCentralCrossRef
3.
Yen H-L, Lipatov AS, Ilyushina NA, Govorkova EA, Franks J, Yilmaz N, Douglas A, Hay A, Krauss S, Rehg JE, Hoffmann E, Webster RG: Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model. J Virol 2001, 81: 6890-6898. 10.1128/JVI.00170-07CrossRef
4.
Tumpey TM, Maines TR, Hoeven NV, Glaser L, Solórzano A, Pappas C, Cox NJ, Swayne DE, Palese P, Katz JM, García-Sastre A: A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission. Science 2007, 315: 655-659. 10.1126/science.1136212PubMedCrossRef
5.
Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y: Avian flu: influenza virus receptors in the human airway. Nature 2006, 440: 435-436. 10.1038/440435aPubMedCrossRef
6.
van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T: H5N1 virus attachment to lower respiratory tract. Science 2006, 312: 399. 10.1126/science.1125548PubMedCrossRef
7.
Bridges CB, Kuehnert MJ, Hall CB: Transmission of influenza: implications for control in health care settings. Clin Infect Dis 2003, 37: 1094-1101. 10.1086/378292PubMedCrossRef
8.
9.
Garner JS: Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1996, 17: 53-80. 10.1086/647190PubMedCrossRef
10.
11.
Cox NJ, Ziegler T: Influenza viruses. In Manual of Clinical Microbiology. 8th edition. Edited by: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH. Washington: ASM Press; 2003:1360-1367.
12.
Hayden FG, Palese P: Influenza virus. In Clinical Virology. 2nd edition. Edited by: Richman DD, Whitley RJ, Hayden FG. Washington: ASM Press; 2002:891-920.
13.
Treanor JJ: Influenza virus. In Mandell, Douglas and Bennett's principles and practice of infectious diseases. 6th edition. Edited by: Mandell GL, Bennett JE, Dolin R. New York: Elsevier Churchill Livingstone; 2005:2060-2085.
14.
Wagner R, Matrosovich M, Klenk HD: Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 2002, 12: 159-166. 10.1002/rmv.352PubMedCrossRef
15.
Wright PF, Webster RG: Orthomyxoviruses. In Fields virology. 4th edition. Edited by: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B. Philadelphia: Lippincott Williams & Wilkins; 2001:1533-1580.
16.
Bean B, Moore BM, Sterner B, Peterson LR, Gerding DN, Balfour HH Jr: Survival of influenza viruses on environmental surfaces. J Infect Dis 1982, 146: 47-51.PubMedCrossRef
17.
The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5: Avian influenza A (H5N1) infection in humans. N Engl J Med 2005, 353: 1374-1385. 10.1056/NEJMra052211CrossRef
18.
Douglas RG: Influenza in man. In The influenza viruses and influenza. Edited by: Kilbourne ED. New York: Academic Press; 1975:375-447.
19.
Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y, Peiris M, Nguyen TD, Hanh TH, Puthavathana P, Long HT, Buranathai C, Lim W, Webster RG, Hoffmann E: Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 2005, 79: 2191-2198. 10.1128/JVI.79.4.2191-2198.2005PubMedPubMedCentralCrossRef
20.
Lipatov AS, Kwon YK, Pantin-Jackwood MJ, Swayne DE: Pathogenesis of H5N1 Influenzavirus infections in mice and ferret models differs according to respiratory tract or digestive system exposure. J Infect Dis 2009, 199: 717-725. 10.1086/596740PubMedCrossRef
21.
Maines TR, Lu XH, Erb SM, Edwards L, Guarner J, Greer PW, Nguyen DC, Szretter KJ, Chen LM, Thawatsupha P, Chittaganpitch M, Waicharoen S, Nguyen DT, Nguyen T, Nguyen HH, Kim JH, Hoang LT, Kang C, Phuong LS, Lim W, Zaki S, Donis RO, Cox NJ, Katz JM, Tumpey TM: Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 2005, 79: 11788-11800. 10.1128/JVI.79.18.11788-11800.2005PubMedPubMedCentralCrossRef
22.
Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM: Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 2002, 76: 4420-4429. 10.1128/JVI.76.9.4420-4429.2002PubMedPubMedCentralCrossRef
23.
24.
Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, Uiprasertkul M, Boonnak K, Pittayawonganon C, Cox NJ, Zaki SR, Thawatsupha P, Chittaganpitch M, Khontong R, Simmerman JM, Chunsutthiwat S: Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005, 352: 333-340. 10.1056/NEJMoa044021PubMedCrossRef
25.
Wang H, Feng Z, Shu Y, Yu H, Zhou L, Zu R, Huai Y, Dong J, Bao C, Wen L, Wang H, Yang P, Zhao W, Dong L, Zhou M, Liao Q, Yang H, Wang M, Lu X, Shi Z, Wang W, Gu L, Zhu F, Li Q, Yin W, Yang W, Li D, Uyeki TM, Wang Y: Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. The Lancet 2008, 371: 1427-1434. 10.1016/S0140-6736(08)60493-6CrossRef
26.
Yang Y, Halloran ME, Sugimoto JD, Longini IM: Detecting human-to-human transmission of avian influenza A (H5N1). Emerg Infect Dis 2007, 9: 1348-1353.CrossRef
27.
Shinya K, Hatta M, Yamada S, Takada A, Watanabe S, Halfmann P, Horimoto T, Neumann G, Kim JH, Lim W, Guan Y, Peiris M, Kiso M, Suzuki T, Suzuki Y, Kawaoka Y: Characterization of a human H5N1 influenza A virus isolated in 2003. J Virol 2005, 79: 9926-9932. 10.1128/JVI.79.15.9926-9932.2005PubMedPubMedCentralCrossRef
28.
Yamada S, Suzuki Y, Suzuki T, Le MQ, Nidom CA, Sakai-Tagawa Y, Muramoto Y, Ito M, Kiso M, Horimoto T, Shinya K, Sawada T, Kiso M, Usui T, Murata T, Lin Y, Hay A, Haire LF, Stevens DJ, Russell RJ, Gamblin SJ, Skehel JJ, Kawaoka Y: Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 2006, 444: 378-382. 10.1038/nature05264PubMedCrossRef
29.
Maher JA, DeStefano J: The ferret: an animal model to study influenza virus. Lab Anim (NY) 2004, 33: 50-53. 10.1038/laban1004-50CrossRef
30.
Herlocher ML, Elias S, Truscon R, Harrison S, Mindell D, Simon C, Monto AS: Ferrets as a transmission model for influenza: sequence changes in HA1 of type A (H3N2) virus. J Infect Dis 2001, 184: 542-546. 10.1086/322801PubMedCrossRef
31.
Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, Monto AS: Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 2004, 190: 1627-1630. 10.1086/424572PubMedCrossRef
32.
Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse-Post DJ, Humberd J, Trichet M, Rehg JE, Webby RJ, Webster RG, Hoffmann E: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006, 203: 689-697. 10.1084/jem.20051938PubMedPubMedCentralCrossRef
33.
World Health Organization Global Influenza Program Surveillance Network: Evolution of H5N1 avian influenza viruses in Asia. Emerg Infect Dis 2005, 11: 1515-1521.CrossRef
34.
World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization H5N1 Evolution Working Group: Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1) [conference summary]. Emerg Infect Dis 2008. [http://​www.​cdc.​gov/​EID/​content/​14/​7/​e1.​htm] --- Either first page or author must be supplied.
35.
Knight V: Airborne transmission and pulmonary deposition of respiratory viruses. In Airborne transmission and airborne infections. 6th International symposium on aerobiology. Edited by: Hers JF, Winkles KC. New York:Wiley; 1973:175-182.
36.
Tuttle RS, Sosna WA, Daniels DE, Hamilton SB, Lednicky JA: Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets. Virol J 2010, 7: e135. 10.1186/1743-422X-7-135CrossRef
37.
Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, Nguyen T, Song P, Le QM, Kawaoka Y: Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice. PLoS Pathog 2007, 3: e133. 10.1371/journal.ppat.0030133PubMedCentralCrossRef
38.
Chen Y, Deng W, Jia C, Dai X, Zhu H, Kong Q, Huang L, Liu Y, Ma C, Li J, Xiao C, Liu Y, Wei Q, Qin C: Pathological lesions and viral localization of Influenza A (H5N1) virus in experimentally infected Chinese rhesus macaques: implications for pathogenesis and viral transmission. Arch Virol 2009, 154: 227-233. 10.1007/s00705-008-0277-5PubMedCrossRef
39.
40.
Szretter KJ, Balish AL, Katz JM: Influenza: Propagation, quantification, and storage. In Current protocols in microbiology. Volume 1. New Jersey: John Wiley & Sons, Inc; 2006. Chapter 15: Unit 15G.1
41.
Reed LJ, Muench H: A simple method for estimating fifty percent endpoints. Am J Hyg 1938, 27: 493-497.
42.
Hamilton SB, Daniels DE, Sosna WA, Jeppesen ER, Owells JM, Halpern MD, McCurdy KS, Rayner JO, Lednicky JA: Gas-permeable ethylene bags for the small scale cultivation of highly pathogenic avian influenza H5N1 and other viruses in embryonated chicken eggs. Virol J 2010, 7: e23. 10.1186/1743-422X-7-23CrossRef
43.
44.
Reuman PD, Keely S, Schiff GM: Assessment of signs of influenza illness in the ferret model. J Virol Methods 1989, 24: 27-34. 10.1016/0166-0934(89)90004-9PubMedCrossRef
45.
Guyton A: Measurements of the respiratory volumes of laboratory animals. Am J Physiol 1947, 150: 70-77.PubMed
46.
Gad SC: Animal Models in Toxicology. Volume Chapter 7. 2nd edition. Edited by: Gad SC. Florida: CRC Press; 2006:493-562.
47.
Vinegar A, Sinnett EE, Kosch PC, Miller ML: Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology. Lab Anim Sci 1985, 35: 246-250.PubMed
48.
Perkins LEL, Swayne DE: Pathobiology of A/chicken/Hong Kong/220/97 (H5N1) avian influenza virus in seven gallinaceous species. Vet Pathol 2001, 38: 149-164. 10.1354/vp.38-2-149PubMedCrossRef
49.
Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR: Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 2001, 146: 2275-2289. 10.1007/s007050170002PubMedCrossRef
50.
Brown JD, Stallknecht DE, Beck JR, Suarez DL, Swayne DE: Susceptibility of North American ducks and gulls to H5N1 highly pathogenic avian influenza viruses. Emerg Infect Dis 2006, 12: 1663-1670.PubMedPubMedCentralCrossRef
Metadata
Title
Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)
Authors
John A Lednicky
Sara B Hamilton
Richard S Tuttle
William A Sosna
Deirdre E Daniels
David E Swayne
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2010
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-7-231

Other articles of this Issue 1/2010

Virology Journal 1/2010 Go to the issue

Methodology

A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle

Research

Development and validation of an ELISA using a protein encoded by ORF2 antigenic domain of porcine circovirus type 2

Research

Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

Research

Synthetic rabbit-human antibody conjugate as a control in immunoassays for immunoglobulin M specific to hepatitis E virus

Research

Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

Research

An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits