Easton, A. J. (Andrew J.), Scott, P. D. (Paul D.), Edworthy, Nicole Lynn, Meng, Bo, Marriott, Anthony C. and Dimmock, N. J.. (2011) A novel broad-spectrum treatment for respiratory virus infections : influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine, Vol.29 (No.15). pp. 2777-2784. ISSN 0264410X

Preview	PDF WRAP_Easton_0380313-lf-310811-easton_et_al_di_protection_revision.pdf - Accepted Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (188Kb)
Preview	Image (TIFF) (Figure 1) WRAP_Easton_Easton_et_al_Fig_1.tif - Accepted Version Download (1957Kb)
Preview	Image (TIFF) (Figure 2) WRAP_easton_Easton_et_al_Fig_2.tif - Accepted Version Download (2098Kb)
Preview	Image (TIFF) (Figure 3) WRAP_Easton_Easton_et_al_Fig_3.tif - Accepted Version Download (1644Kb)
Preview	Image (TIFF) (Figure 4) WRAP_Easton_Easton_et_al_Fig_4.tif - Accepted Version Download (3016Kb)
Preview	Image (TIFF) (Figure 5) WRAP_easton_Easton_et_al_Fig_5.tif - Accepted Version Download (958Kb)
Preview	Image (TIFF) (Figure 6) WRAP_easton_Easton_et_al_Fig_6.tif - Accepted Version Download (1028Kb)

Abstract

Respiratory viruses represent a major clinical burden. Few vaccines and antivirals are available, and the rapid appearance of resistant viruses is a cause for concern. We have developed a novel approach which exploits defective viruses (defective interfering (DI) or protecting viruses). These are naturally occurring deletion mutants which are replication-deficient and multiply only when coinfection with a genetically compatible infectious virus provides missing function(s) in trans. Interference/protection is believed to result primarily from genome competition and is therefore usually confined to the virus from which the DI genome originated. Using intranasally administered protecting influenza A virus we have successfully protected mice from lethal in vivo infection with influenza A viruses from several different subtypes [1]. Here we report, contrary to expectation, that protecting influenza A virus also protects in vivo against a genetically unrelated respiratory virus, pneumonia virus of mice, a pneumovirus from the family Paramyxoviridae. A single dose that contains 1 μg of protecting virus protected against lethal infection. This protection is achieved by stimulating type I interferon and possibly other elements of innate immunity. Protecting virus thus has the potential to protect against all interferon-sensitive respiratory viruses and all influenza A viruses.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Respiratory infections -- Treatment, Antiviral agents, Paramyxoviruses, Influenza A virus
Journal or Publication Title:	Vaccine
Publisher:	Elsevier BV
ISSN:	0264410X
Date:	24 March 2011
Volume:	Vol.29
Number:	No.15
Page Range:	pp. 2777-2784
Identification Number:	10.1016/j.vaccine.2011.01.102
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Medical Research Council (Great Britain) (MRC), Mercia Spinner
References:	[1] Dimmock NJ, Rainsford EW, Scott PD, Marriott AC. Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral. J Virol 2008;82:8570-8. [2] Lamb RA, Krug RM. Orthomyxoviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM, editors. Fields Virology. 3 ed. Philadelphia: Lippincott-Raven Publishers, 1996: 1353-95. [3] Lamb RA, Kolakofsky D. Paramyxoviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM, editors. Fields Virology. 3 ed. Philadelphia: Lippincott-Raven Publishers, 1996: 1177-204 [4] Sheu TG, Deyde VM, Okomo-Adhiambo M, Garten RJ, Xu X, Bright RA, et al. Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother 2008;52:3284–92. [5] Besselaar TG, Naidoo D, Buys A, Gregory V, McAnerney J, Manamela JM, et al. Widespread oseltamivir resistance in influenza A viruses (H1N1), South Africa. Emerging Infect Dis 2008;14:1809–10. [6] The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1996;102:531-7. [7] Holland JJ. Generation and replication of defective viral genomes. In: Fields BN, Knipe DM, editors. Virol. 2nd ed. New York: Raven Press, 1990: 77-99. [8] Huang AS, Baltimore D. Defective viral particles and viral disease processes. Nature (Lond) 1970;226:325-7. [9] Perrault J. Origin and replication of defective interfering particles. Curr Topics Microbiol Immunol 1981;93:151-207. [10] Nayak DP, Chambers TM, Akkina RM. Structure of defective-interfering RNAs of influenza virus and their role in interference. In: Krug RM, editor. The Influenza Viruses. New York: Plenum Press, 1989: 269-317. [11] Holland JJ. Defective viral genomes. In: Fields BN, Knipe DM, editors. Virol. 2nd ed. New York: Raven Press, 1990: 151-65. [12] von Magnus P. Incomplete forms of influenza virus. Adv Virus Res 1954;21:59-79. [13] von Magnus P. Studies on interference in experimental influenza. I. Biological observations. Arkiv fur Kemi, Mineralogi och Geologi 1947;24b:1-6. [14] Gard S, von Magnus P. Studies on interference in experimental influenza. II Purification and centrifugation experiments. Arkiv fur Kemi, Mineralogi och Geologi 1947;24b:1-4. [15] Nayak DP. Influenza virus defective interfering particles. Ann Rev Microbiol 1980;34:619-44. [16] Nayak DP, Chambers TM, Akkina RK. Defective-interfering (DI) RNAs of influenza viruses: origin, structure, expression and interference. Curr Topics Microbiol Immunol 1985;114:103-51. [17] 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;34:619-27. [18] 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. Virol 1998;248:241-53. [19] Duhaut S, Dimmock NJ. Approximately 150 nt from the 5' end of an influenza A virus segment 1 defective virion RNA are needed for genome stability during passage of defective virus in infected cells. Virol 2000;275:278-85. [20] Duhaut SD, Dimmock NJ. Defective segment 1 RNAs that interfere with the production of infectious influenza virus require at least 150 nucleotides of 5' sequence: evidence from a plasmid-driven system. J Gen Virol 2002;83:403-11. [21] Duhaut SD, Dimmock NJ. Defective influenza A virus generated entirely from plasmids: its RNA is expressed in infected mouse lung and modulates disease. J Virol Meth 2003;108:75-82. [22] Marriott AC, Dimmock NJ. Defective interfering viruses and their potential as antiviral agents. Rev Med Virol 2010;20:51-62. [23] Roux L, Simon AE, Holland JJ. Effects of defective interfering viruses on viral replication and pathogenesis in vitro and in vivo. Adv Virus Res 1991;40:181-211. [24] Dimmock NJ. Antiviral activity of defective interfering influenza virus in vivo. In: Myint S, Taylor-Robinson D, editors. Viral and Other Infections of the Respiratory Tract. London: Chapman and Hall, 1996: 421-45. [25] Dimmock NJ. The biological significance of defective interfering viruses. Rev Med Virol 1991;1:165-76. [26] Barrett ADT, Dimmock NJ. Defective interfering viruses and infections of animals. Curr Topics Microbiol Immunol 1986;128:55-84. [27] Marcus PI, Gaccione C. Interferon induction by viruses. XIX Vesicular stomatitis virus-New Jersey: high multiplicity passages generate interferon-inducing, defective-interfering particles. Virol 1989;171:630-3. [28] Marcus PI, Sekellick MJ. Defective interfering particles with covalently linked +RNA induce interferon. Nature (Lond) 1977;266:815-9. [29] Sekellick MJ, Marcus PI. Interferon induction by viruses. VIII Vesicular stomatitis virus: [+/-] DI-011 particles induce interferon in the absence of standard virions. Virol 1982;117:280-5. [30] Strahle L, Garcin D, Kolakofsky D. Sendai defective-interfering genomes and the activation of interferon-beta. Virol 2006;351:101-11. [31] Frey TK, Jones EV, Cardamone JJ, Youngner JS. Induction of interference in L cells by defective-interfering (DI) particles of vesicular stomatitis virus: lack of correlation with content of [+/-] snapback RNA. Virol 1979;99:95-102. [32] Baum A, Sachidanandam R, García-Sastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proceedings of the National Academy of Science of the United States of America 2010;107:16303-8. [33] Easton AJ, Domachowske JB, Rosenberg JF. Animal pneumoviruses: molecular genetics and pathogenesis. Clin Microbiol Revs 2004;17:390-412. [34] Pringle CR, Eglin RP. Murine pneumonia virus: seroepidemiological evidence of widespread human infection. J Gen Virol 1986;67:975-82. [35] Noble S, Dimmock NJ. Defective interfering type A equine influenza virus (H3N8) protects mice from morbidity and mortality caused by homologous and heterologous subtypes of type A influenza virus. J Gen Virol 1994;75:3485-91. [36] Noble S, McLain L, Dimmock NJ. Interfering vaccine: a novel antiviral that converts a potentially virulent infection into one that is subclinical and immunizing. Vaccine 2004;22:3018-25. [37] Cook PM, Eglin RP, Easton AJ. Pathogenesis of pneumovirus infections in mice: detection of pneumonia virus of mice and human respiratory syncytial virus mRNA in lungs of infected mice by in situ hybridization. J Gen Virol 1998;79:2411-4217. [38] Barr J, Chambers P, Harriott P, Pringle CR, Easton AJ. Sequence of the phosphoprotein gene of pneumonia virus of mice: expression of multiple proteins from two overlapping reading frames. J Virol 1994;68:5330-4. [39] Beilharz MW, Cummins JM, Bennett AL. Protection from lethal influenza virus challenge by oral type 1 interferon. Biochem Biophys Res Commun 2007;355:740-4. [40] Tumpey TM, Szretter KJ, Van Hoeven N, Katz JM, Kochs G, Haller O, et al. The Mx1 gene protects mice against the pandemic 1918 and highly lethal human H5N1 influenza viruses. J Virol 2007;81:10818-21. [41] Kugel D, Kochs G, Obojes K, Roth J, Kobinger GP, Kobasa D, et al. Intranasal administration of α interferon reduces seasonal influenza A virus morbidity in ferrets. J Virol 2009;83:3843-51. [42] Gao L, Yu S, Chen Q, Duan Z, Zhou J, Mao C, et al. A randomized controlled trial of low-dose recombinant human interferons alpha-2b nasal spray to prevent acute viral respiratory infections in military recruits. Vaccine 2010;28:4445-51. [43] Katze MG, He Y, Gale M. Viruses and interferon: a fight for supremacy. Nature (Lond) 2002;419:6902-. [44] Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (alpha/beta) in immunity and autoimmunity. Ann Rev Immunol 2005;23:307-36. [45] Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and countermeasures. J Gen Virol 2008;89:1-47.
URI:	http://wrap.warwick.ac.uk/id/eprint/37174

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item