The Library

Defective interfering virus protects elderly mice from influenza

Tools

Scott, P. D. (Paul D.), Meng, Bo, Marriott, Anthony C., Easton, A. J. (Andrew J.) and Dimmock, N. J.. (2011) Defective interfering virus protects elderly mice from influenza. Virology Journal, Vol.8 (No.212). ISSN 1743-422X

Preview

PDF
WRAP_Dimmock_1743-422X-8-212.pdf - Published Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1352Kb)

Official URL: http://dx.doi.org/10.1186/1743-422X-8-212

Abstract

Background: We have identified and characterised a defective-interfering (DI) influenza A virus particles containing a highly deleted segment 1 RNA that has broad-spectrum antiviral activity. In young adult mice it exerts protection against several different subtypes of influenza A virus (defined here as homologous or genetically compatible protection) and against a paramyxovirus and an influenza B virus (heterologous or genetically unrelated protection). Homologous protection is mediated by replication competition between the deleted and full-length genomes, and heterologous protection occurs through stimulation of innate immunity, especially interferon type I. Methods: A single dose of the protective DI virus was administered intranasally to elderly mice at -7, -1 and +1 days relative to intranasal challenge with influenza A virus. Results: A single dose of the DI virus given 1 or 7 days protected elderly mice, reducing a severe, sometimes fatal disease to a subclinical or mild infection. In contrast, all members of control groups treated with inactivated DI virus before challenge became extremely ill and most died. Despite the subclinical/mild nature of their infection, protected mice developed solid immunity to a second infectious challenge. Conclusions: The defective interfering virus is effective in preventing severe influenza A in elderly mice and may offer a new approach to protection of the human population.

[error in script] [error in script]

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Influenza -- Prevention, Influenza A virus, Antiviral agents
Journal or Publication Title:	Virology Journal
Publisher:	BioMed Central Ltd.
ISSN:	1743-422X
Date:	9 May 2011
Volume:	Vol.8
Number:	No.212
Identification Number:	10.1186/1743-422X-8-212
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC)
References:	1. Treanor JJ, Falsey A: Respiratory viral infections in the elderly. Antiviral Research 1999, 44:79-102. 2. Webster RG: Immunity to influenza in the elderly. Vaccine 2000, 18:1686-1689. 3. Falsey A, Dallal G, Formica M, Andolina G, Hamer D, Leka L, Meydani S: Long-term care facilities: A cornucopia of viral pathogens. Journal of the American Geriatrics Society 2008, 56:1281-1285. 4. Yoshikawa TT, Norman DC: Infectious disease in the aging Towota, NJ: Humana Press; 2000. 5. Canaday D, Amponsah N, Jones L, Tisch D, Hornick T, Ramachandra L: Influenza-induced production of interferon-α is defective in geriatric individuals. Journal of Clinical Immunology 2010, 30:373-383. 6. Fujihashi K, Koga T, McGhee JR: Mucosal vaccination and immune responses in the elderly. Vaccine 2000, 18:1675-1680. 7. Fulop T, Pawelec G, Castle S, Loeb M: Immunosenescence and vaccination in nursing home residents. Clinical Infectious Diseases 2009, 48:443-448. 8. Huang YP, Pechere JC, Michel M, Gauthey L, Loreto M, Curran JA, Michel JP: In vivo T cell activation, in vitro defective IL-2 secretion, and response to influenza vaccination in elderly women. Journal of Immunology 1992, 148:715-722. 9. Joshi SR, Shaw AC, Quagliarello VJ: Pandemic influenza H1N1 2009, innate immunity, and the impact of immunosenescence on influenza vaccine. Yale Journal of Biology and Medicine 2009, 82:143-151. 10. Kovaiou RD, Grubeck-Loebenstein B: Age-associated changes within CD4+ T cells. Immunology Letters 2006, 107:8-14. 11. Mbawuike IN, Lange AR, Couch RB: Diminished influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte activity among elderly persons. Viral Immunology 1993, 6:55-64. 12. Reis e Sousa C: Dendritic cells in a mature age. Nature Reviews in Immunology 2007, 6:476-483. 13. Romero-Steiner S, Musher DM, Cetron MS, Pais LB, Groover JE, Fiore AE, Plikaytis BD, Carlone GM: Reduction in functional antibody activity against Streptococcus pneumoniae in vaccinated elderly individuals highly correlates with decreased IgG antibody avidity. Clinical and Infectious Disease 1999, 29:281-288. 14. Vallejo AN: Age-dependent alterations of the T cell repertoire and functional diversity of T cells of the aged. Immunological Research 2007, 36:221-228. 15. Whitley RJ, Monto AS: Prevention and treatment of influenza in high-risk groups: children, pregnant women, immunocompromised hosts, and nursing home residents. Journal of Infectious Diseases 2006, 194(S2): S133-S138. 16. Elliot A, Fleming D: Influenza and respiratory syncytial virus in the elderly. Expert Review of Vaccines 2008, 7:249-258. 17. Cox NJ, Subbarao K: Influenza. The Lancet 1999, 354:1277-1282. 18. Wilson IA, Cox NJ: Structural basis of immune recognition of influenza virus hemagglutinin. Annual Review of Immunology 1990, 8:737-771. 19. Gross PA, Hermogenes A, Sacks HS, Lau J, Levandowski RA: The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Annals of Internal Medicine 1995, 123:518-527. 20. Jefferson T, Rivetti D, Rudin M, Di Pietrantonj C, Demicheli V: Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 2005, 366:1165-1174. 21. Goodwin K, Viboud C, Simonsen L: Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 2006, 24:1159-1169. 22. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE: Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010, 2(2):CD004876. 23. Jefferson T, Jones M, Doshi P, Del Mar C, Dooley L, Foxlee R: Neuraminidase inhibitors for preventing and treating influenza in healthy adults. Cochrane Database of Systematic Reviews, Issue 2, article number CD001265 2010. 24. McKimm-Breschkin JL, Selleck PW, Usman TB, Johnson MA: Influenza (H5N1) with decreased oseltamivir sensitivity, Indonesia. Emerging Infectious Diseases 2007, 13:1354-1357. 25. Monto A: Implications of antiviral resistance of influenza viruses. Clinical Infectious Diseases 2009, 48:397-399. 26. Aoki FY, Boivin G, Roberts N: Influenza virus susceptibility and resistance to oseltamivir. Antiviral Therapy 2007, 12:603-616. 27. Holland JJ: Defective viral genomes. In Virology. Volume 1.. 2 edition. Edited by: Fields BN, Knipe DM. New York: Raven Press; 1990:151-165. 28. Holland JJ: Generation and replication of defective viral genomes. In Virology.. 2 edition. Edited by: Fields BN, Knipe DM. New York: Raven Press; 1990:77-99. 29. Huang AS, Baltimore D: Defective viral particles and viral disease processes. Nature (London) 1970, 226:325-327. 30. Nayak DP, Chambers TM, Akkina RM: Structure of defective-interfering RNAs of influenza virus and their role in interference. In The Influenza Viruses. Edited by: Krug RM. New York: Plenum Press; 1989:269-317. 31. Perrault J: Origin and replication of defective interfering particles. Current Topics in Microbiology and Immunology 1981, 93:151-207. 32. von Magnus P: Incomplete forms of influenza virus. Advances in Virus Research 1954, 21:59-79. 33. Nayak DP, Chambers TM, Akkina RK: Defective-interfering (DI) RNAs of influenza viruses: origin, structure, expression and interference. Current Topics in Microbiology and Immunology 1985, 114:103-151. 34. Jennings PA, Finch JT, Winter G, Robertson JS: Does the higher order of the influenza virus ribonucleoprotein guide sequence rearrangements in influenza viral RNA. Cell 1983, 34:619-627. 35. Duhaut SD, Dimmock NJ: Heterologous protection against a lethal human H1N1 influenza virus infection of mice by a H3N8 equine defective interfering virus: comparison of defective RNA sequences isolated from the DI inoculum and mouse lung. Virology 1998, 248:241-253. 36. Dimmock NJ, Rainsford EW, Scott PD, Marriott AC: Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral. Journal of Virology 2008, 82:8570-8578. 37. Marriott AC, Dimmock NJ: Defective interfering viruses and their potential as antiviral agents. Reviews in Medical Virology 2010, 20:51-62. 38. Toapanta FR, Ross TM: Impaired immune responses in the lungs of aged mice following influenza infection. Respiratory Research 2009, 10:112. 39. Wen ZY, Ye L, Gao YL, Pan L, Dong K, Bu ZG, Compans RW, Yang CL: Immunization by influenza virus-like particles protects aged mice against lethal influenza virus challenge. Antiviral Research 2009, 84:215-224. 40. Dong L, Mori I, Hossain MJ, Kimura Y: The senescence-accelerated mouse shows aging-related defects in cellular but not humoral imunity against influenza virus. Journal of Infectious Diseases 2000, 182:391-396. 41. Dong L, Mori I, Hossain MJ, Liu B, Kimura Y: An immunostimulatory oligodeooxynucleotide containing a cytidine-guanosine motif protects senescence-accelerated mice from lethal influenza virus by augmenting the T helper type 1 response. Journal of General Virology 2003, 84:1623-1628. 42. Effros RB, Walford RL: The immune response of aged mice to influenza: diminished T-cell proliferation, interleukin 2 production and cytotoxicity. Cellular Immunolology 1983, 81:298-305. 43. Po JL, Gardner EM, Anaraki F, Katsikis PD, Murasko DM: Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection. Mechanisms of Ageing and Development 2002, 123:1167-1181. 44. Zheng B, Zhang Y, He H, Marinova E, Switzer K, Wansley D, Mbawuike I, Han S: Rectification of age-associated deficiency in cytotoxic T cell response to influenza A virus by immunization with immune complexes. Journal of Immunology 2007, 179:6153-6159. 45. Easton AJ, Scott PD, Edworthy NL, Meng B, Marriott AC, Dimmock NJ: A novel broad-spectrum treatment for respiratory virus infections: influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine 2011, 29:2777-2784.
URI:	http://wrap.warwick.ac.uk/id/eprint/35503