MOUSE MODEL FOR THE STUDY OF ATTENUATION OF COLD-ADAPTED INFLUENZA VIRUSES



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Animal models of influenza infection are crucial to understanding of mechanisms of attenuation of cold-adapted (ca) influenza viruses. Ferrets are a common model for study of pathogenesis of influenza infection and evaluation of attenuation of ca live influenza vaccine (LAIV). A number of ca master donor viruses (MDVs) for LAIV exist which are different by number and localization of attenuating mutations. All known MDVs are attenuated for ferrets. However, this animal model is not sufficient to estimate detailed differences in attenuation level of different MDVs. Objective of the study was to search for an animal model that allows revealing in vivo subtle differences in the level of attenuation of different MDVs. BALB/c female mice and female ferrets were inoculated intranasally with wild-type and ca influenza viruses. Virus isolation from nasal turbinated or nasal washes and/or lung tissue was performed in embryonated chicken eggs. Wild-type influenza viruses multiplied both in upper (URT) and lower (LRT) respiratory tract of ferrets. In contrast, ca LAIV strains and MDVs lost the ability to replicate in the LRT with a pronounced reproduction in URT. Unlike ferrets, on a mouse model, more attenuated influenza viruses reproduced in the LRT less actively than less attenuated variants. More attenuated ca viruses, which contains more attenuating mutations, demonstrated lower infectious titers in mice LRT compared to less attenuated viruses. A correlation between attenuation level of ca viruses and the severity of their reproduction in the mice lungs was established. This finding allows us to consider mice as a model for studying the level of attenuation of ca influenza viruses.

Full Text

Restricted Access

About the authors

I V Kiseleva

Institute of Experimental Medicine

E V Krutikova

Institute of Experimental Medicine

A R Rekstin

Institute of Experimental Medicine

K L Kryshen

Institute of Pre-Clinical Research Ltd

L G Rudenko

Institute of Experimental Medicine

References

  1. Barnard D.L. Animal models for the study of influenza pathogenesis and therapy // Antiviral Res. 2009. Vol. 82, Nо 2. P. 110-122.
  2. Bouvier N.M., Lowen A.C. Animal models for influenza virus pathogenesis and transmission // Viruses. 2010. Vol. 2. P. 1530-1563.
  3. Oh D.Y, Hurt A.C. Using the ferret as an animal model for investigating influenza antiviral effectiveness // Front Microbiol. 2016. Vol. 7, Nо 80. P. 1-12.
  4. Gabor K.A., Goody M.F., Mowel W.K., Breitbach M.E., Gratacap R.L., Witten P.E., Kim C.H. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment // Dis Model Mech. 2014. Vol. 7, Nо 11. P. 1227-1237.
  5. Goody M.F., Sullivan C., Kim C.H. Studying the immune response to human viral infections using zebrafish // Dev Comp Immunol. 2014. Vol. 46, Nо 1. P. 84-95.
  6. Matsuoka Y., Lamirande E.W., Subbarao K. The ferret model for influenza // Curr Protoc Microbiol. 2009. Vol. 15G, Nо 2. doi: 10.1002/9780471729259.
  7. Belser J.A., Katz J.M., Tumpey T.M. The ferret as a model organism to study influenza A virus infection // Dis Model Mech. Vol. 4, Nо 5. P. 575-579.
  8. Thangavel R.R., Bouvier N.M. Animal models for influenza virus pathogenesis, transmission, and immunology // J. Immunol. Methods. 2014. Vol. 410. P. 60-79.
  9. Enkirch T., von Messling V. Ferret models of viral pathogenesis // Virology. 2015. Vol. 479-480. P. 259-270.
  10. Belser J.A., Eckert A.M., Tumpey T.M., Maines T.R. Complexities in ferret influenza virus pathogenesis and transmission models // Microbiol. Mol. Biol. Rev. 2016. Vol. 80, N 3. P. 733-744.
  11. WHO Biosafety risk assessment and guidelines for the production and quality control of human influenza pandemic vaccines. In WHO Expert Committee on Biological Standardization. Fifty-sixth report. Geneva, World Health Organization, 2005, Annex 5 (WHO Technical Report Series, No. 941) // Электрон. дан. режим доступа URL: http://www.who.int/biologicals/publications/trs/areas/vaccines/influenza/Annex%205%20human%20pandemic%20influenza.pdf (дата обращения 01.05.2017).
  12. Palker T., Kiseleva I., Johnston K., Su Q., Toner T., Szymkowiak C., Kwan W.S., Rubin B., Petrukhin L., Wlochowski J., Monteiro J., Kraiouchkine N., DiStefano D., Rudenko L., Shaw A., Youil R. Protective efficacy of intranasal cold-adapted influenza A/New Caledonia/20/99 (H1N1) vaccinescomprised of egg- or cell culture-derived reassortants // Virus Res. 2004. Vol. 105, Nо 2. P. 183-194.
  13. Stittelaar K.J., Veldhuis Kroeze E.J., Rudenko L., Dhere R., Thirapakpoomanunt S., Kieny M.P., Osterhaus A.D. Efficacy of live attenuated vaccines against 2009 pandemic H1N1 influenza in ferrets // Vaccine. 2011. Vol. 29, Nо 49. P. 9265-9270.
  14. De Jonge J., Isakova-Sivak I., van Dijken H., Spijkers S., Mouthaan J., de Jong R., Smolonogina T., Roholl P., Rudenko L. H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets // Mol Ther. 2016. Vol. 24, Nо 5. P. 991-1002.
  15. Larionova N., Kiseleva I., Isakova-Sivak I., Rekstin A., Dubrovina I., Bazhenova E., Ross T.M., Swayne D., Gubareva L., Tsvetnitsky V., Fedorova E., Doroshenko E., Rudenko L. Live attenuated influenza vaccines against highly pathogenic H5N1avian influenza: Development and preclinical characterization // J Vaccines Vaccin. 2013. Vol. 4, Nо 8. doi: 10.4172/2157-7560.1000208.
  16. Mann A.J., Noulin N., Catchpole A., Stittelaar K.J., de Waal L., Veldhuis Kroeze E.J., Hinchcliffe M., Smith A., Montomoli E., Piccirella S., Osterhaus A.D., Knight A., Oxford J.S., Lapini G., Cox R., Lambkin-Williams R. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highlypathogenic influenza intranasal and intratracheal challenge // PLoS One. 2014. Vol. 9, Nо 5. e93761.
  17. Rekstin A., Desheva Y., Kiseleva I., Ross T., Swayne D., Rudenko L. Live Attenuated Influenza H7N3 Vaccine is Safe, Immunogenic and Confers Protection in AnimalModels // Open Microbiol J. 2014. Vol. 8 P. 154-162.
  18. Isakova-Sivak I., de Jonge J., Smolonogina T., Rekstin A., van Amerongen G., van Dijken H., Mouthaan J., Roholl P., Kuznetsova V., Doroshenko E., Tsvetnitsky V., Rudenko L. Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus // PLoS One. 2014. Vol. 9, Nо 7. e102339.
  19. Major D., Chichester J.A., Pathirana R.D., Guilfoyle K., Shoji Y., Guzman C.A., Yusibov V., Cox R.J. Intranasal vaccination with a plant derived H5 HA vaccine protects mice and ferrets againsthighly pathogenic avian influenza virus challenge // Hum Vaccin Immunother. 2015. Vol. 11, Nо 5. P. 1235-1343.
  20. Matsuoka Y., Lamirande E.W., Subbarao K. The ferret model for influenza // Curr Protoc Microbiol. 2009. 15G.3. doi: 10.1002/9780471729259.mc15g03s13.
  21. WHO. Global influenza pandemic action plan to increase vaccine supply. Geneva, Belgium. WHO/IVB/06.13. WHO/ODS/EPR/GIP/2006.1. 2006 // Электрон. дан. режим доступа URL: http://whqlibdoc.who.int/hq/2006/WHO_IVB_06.13_eng.pdf.http://whqlibdoc.who.int/hq/2006/WHO_IVB_06.13_eng.pdf (дата обращения 01.05.2017)
  22. WHO. Global influenza preparedness plan. WHO/CDS/CSR/GIP/2005.5. 2005 // Электрон. дан. режим доступа URL: www.who.int/csr/resources/publications/influenza/en/WHO_CDS_CSR_GIP_2005_5.pdf (дата обращения 01.05.2017).
  23. WHO Expert Committee on Biological Standardization. 60th report. Annex 4. WHO recommendations to assure the quality, safety and efficacy of influenza vaccines (human, live attenuated) for intranasal administration // Электрон. дан. режим доступа URL: http://www.who.int/biologicals/areas/vaccines/influenza/TRS_977_Annex_4.pdf?ua=1 (дата обращения 01.05.2017).
  24. Klimov A.I., Cox N.J., Yotov W.V., Rocha E., Alexandrova G.I., Kendal A.P. Sequence changes in the live attenuated, cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus // Virology. 1992. Vol. 186, Nо 2. P. 795-797.
  25. Isakova-Sivak I., Chen L.M., Matsuoka Y., Voeten J.T.M., Kiseleva I., Heldens J.G.M., Van den Bosch H., Klimov A., Rudenko .L, Cox N.J., Donis R.O. Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2) // Virology. 2011. Vol. 412, Nо 2. P. 297-305.
  26. Kiseleva I., Voeten J.T.M., Teley L.C.P., Larionova N., Drieszen-van der Cruijsen S.K.M., Basten S.M.C., Heldens J.G.M., van den Bosch J.F., Rudenko L. PB2 and PA genes control the expression of the temperature sensitive phenotype of cold-adapted B/USSR/60/69 influenza master donor virus // J. Gen. Virol. 2010. Vol. 91. P. 931-937.
  27. Klimov A.I., Kiseleva I.V., Alexandrova G.I., Cox N.J. Genes coding for polymerase proteins are essential for attenuation of the cold-adapted A/Leningrad/134/17/57 (H2N2) influenza virus // International Congress Series. 2001. Vol. 1219. P. 955-959.
  28. Reed L.J., Muench H. A simple method of estimating fifty per cent endpoints // Amer. J. Hyg. 1938. Vol. 27. P. 493-497.
  29. Bhardwaj S., Gupta D. Study of acute, sub acute and chronic toxicity test // IJARPB. 2012. Vol. 2, Nо 2. P. 103-129.
  30. Carolan A.L., Rockman S., Borg K., Guarnaccia T., Reading P., Mosse J., Kelso A., Barr L., Lauriea L.K. Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses // J. Virol. 2016. Vol. 90, Nо 6. P. 2838-2848.
  31. Schulman J.L., Kilbourne E.D. Experimental transmission of influenza virus infection in mice. I. The period of transmissibility // J. Exp. Med. 1963. Vol. 118. P. 257-266.
  32. Schulman J.L., Kilbourne E.D. Experimental transmission of influenza virus infection in mice. II. Some factors affecting the incidence of transmitted infection // J. Exp. Med. 1963. Vol. 118. P. 267-275.
  33. Schulman J.L. Experimental transmission of influenza virus infection in mice III. Differing effects of immunity induced infection and by inactivated influenza virus vaccine on transmission of infection // J. Exp. Med. 1967. Vol. 125, Nо 3. P. 467-478.
  34. Schulman J.L. Experimental transmission of influenza virus infection in mice IV. Relationship of transmissibility of different strains of virus and recovery of airborne virus in the environment of infector mice // J. Exp. Med. 1967. Vol. 125, Nо 3. P. 479-488.
  35. Lowen A.C., Mubareka S., Tumpey T.M., García-Sastre A., Palese P. The guinea pig as a transmission model for human influenza viruses // Proc. Natl. Acad. Sci. USA. 2006. Vol. 103. P. 9988-9992.
  36. Lowen A.C., Steel J., Mubareka S., Carnero E., Garcia-Sastre A., Palese P. Blocking inter-host transmission of influenza virus by vaccination in the guinea pig model // J. Virol. 2009. Vol. 83. P. 2803-2818.
  37. Григорьева Е.П., Дешева Ю.А., Донина С.А., Найхин А.Н., Рекстин А.Р., Баранцева И.Б., Завиткова Е.А., Москвичева Т.М., Жаворонков В.Г., Руденко Л.Г. Сравнительная оценка безвредности, иммуногенной активности и профилактической эффективности взрослого и детского вариантов живой гриппозной вакцины у школьников 7-14 лет при стандартных схемах введения. Вопросы вирусологии // Вопросы вирусологии. 2002. T. 47, вып. 4. С. 24-27. [Grigorieva E.P., Desheva I., Donina S.A., Naikhin A.N., Rekstin A.R., Barantseva I.B. The comparative characteristics of the safety, immunogenic activity and prophylactic potency of the adult and children types of live influenza vaccine in schoolchildren aged 7-14 years, Vopr. Virusol. Vol. 47 (4). pp. 24-27.]
  38. Дешева Ю.А., Данини Г.В., Григорьева Е.П., Донина С.А., Киселева И.В., Рекстин А.Р., Ермакова Л.А., Нацина В.К., Николаева В.М., Лонская Н.И., Епишина Г.А., Жаворонков В.Г., Дриневский В.П., Ерофеева М.К., Найхин А.Н., Руденко Л.Г. Изучение безвредности, генетической стабильности и иммуногенности живой гриппозной вакцины для взрослых при вакцинации детей 3-6 лет // Вопросы вирусологии. 2002. Т. 47, вып. 4. C. 21-24. [Desheva Iu.A., Danini G.V., Grigor'eva E.P., Donina S.A., Kiseleva I.V., Rekstin A.R., Ermakova L.A., Natsina V.K., Nikolaeva V.M., Lonskaia N.I., El'shina G.A., Zhavoronkov V.G., Drinevskii V.P., Erofeeva M.K., Naikhin A.N., Rudenko L.G. The investigation of the safety, genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children, Vopr. Virusol. 2002. Vol. 47 (4). pp. 21-24.]
  39. Lu X., Edwards L.E., Desheva J.A., Nguyen D.C., Rekstin A., Stephenson I., Szretter K., Cox N.J., Rudenko L.G., Klimov A., Katz J.M. Cross-protective immunity in mice induced by live-attenuated or inactivated vaccines against highly pathogenic influenza A (H5N1) viruses // Vaccine. 2006. Vol. 24. P. 6588-6593.
  40. Lu X., Tumpey T.M., Morken T., Zaki S.R., Cox N.J., Katz J.M. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans // J. Virol. 1999. Vol. 73, Nо 7. P. 5903-5911.
  41. Chen J.R., Yua Y.H., Tsenga Y.C., Chianga W.L., Chianga M.F., Koa Y.A., Chiua Y.K., Maa H.H., Wua C.Y., Jana J.T., Lina K.I., Maa C., Wonga C.H. Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections // PNAS. 2014. Vol. 111, Nо 7. P. 2471-2481.
  42. Рекстин А.Р., Лу К., Кац Д., Руденко Л.Г. Особенности продукции ранних цитокинов in vivo после инфицирования вирусом гриппа А/Ленинград/134/57 (H2N2) и его холодоадаптированными аттенуированными вариантами // Вопросы вирусологии. 2006. Т. 51, Вып. 2. С. 27-30. [Rekstin A.R., Lu K., Kats D., Rudenko L.G. The specific features of in vivo production of early cytokines after infection with A/Leningrad/134/57 (H2N2) wide-type virus and cold-adapted attenuated vaccine viruses, Vopr. Virusol. 2006. Vol. 51 (2). pp. 27-30].
  43. Middleton D., Rockman S., Pearse M., Barr I., Lowther S., Klippel J., Ryan D., Brown L. Evaluation of vaccines for H5N1 Influenza virus in ferrets reveals the potential for protective single-shot immunizationn // J. Virol. 2009. Vol. 83, Nо 15. P. 7770-7778.
  44. Huang S.S.H., Banner D., Paquette S.G., Leon A.J., Kelvin A.A., Kelvin D.J. Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection // J Gen Virol. 2014. V. 95 P. 2127-2139.
  45. Paquette S.G., Banner D., Huang S.S.H., Almansa R., Leon A., Xu L., Bartoszko J., Kelvin D.J., Kelvin A.A. Influenza transmission in the mother-infant dyad leads to severe disease, mammary gland infection, and pathogenesis by regulating host responses // PLoS Pathog. 2015. Vol. 11, Nо 10. e1005173.
  46. Xu L., Bao L., Deng W., Zhu H., Chen T., Lv Q., Li F., Yuan J., Xiang Z., Gao K., Xu Y., Huang L., Li Y., Liu J., Yao Y., Yu P., Yong W., Wei Q., Zhang L., Qin C. The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus // Virol J. 2013. Vol. 10. P. 253.
  47. Broadbent A.J., Santos C.P., Anafu A., Wimmer E., Mueller S., Subbarao K. Evaluation of the attenuation, immuneogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets // Vaccine. 2016. Vol. 34, Nо 4. P. 563-570.
  48. Pascua P.N.Q., Marathe B.M., Burnham A.J., Vogel P., Webby R.J., Webster R.G., Govorkova E.A. Competitive fitness of influenza B viruses possessing E119A and H274Y neuraminidase inhibitor resistance-associated substitutions in ferrets // PLoS One. 2016. doi: 10.1371/journal.pone.0159847.
  49. Russier M., Yang G., Marinova-Petkova A., Vogel P., Kaplan B.S., Webby R.J., Russell C.J. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets // PLoS Pathog. 2017. Vol. 13, No 3. e1006276.
  50. Kim E.H., Park S.J., Kwon H.I., Kim S.M., Kim Y.I., Song M.S., Choi E.J., Pascua P.N.Q., Choi Y.K. Mouse adaptation of influenza B virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets. Scientific Reports // Scientific Reports. 2015. Vol. 5. Р. 15940. DOI: 10.1038.
  51. Крутикова Е.В., Киселева И.В., Федорова Е.А., Дубровина И.А., Руденко Л.Г. Холодоадаптированный вирус B/Ленинград/14/17/55 - альтернативный донор аттенуации живой гриппозной вакцины для детей младшего возраста // Медицинский академический журнал. 2016. Т. 16, вып. 4. С. 156-157. [Krutikova E.V., Kiseleva I.V., Fedorova E.A., Dubrovina I.A., Rudenko L.G. Cold-adapted B/Leningrad/14/17/57 influenza strain as a backup master donor virus for live attenuated influenza vaccine for young children, Medical Academic Journal. 2016. Vol. 16 (4). pp. 156-157.]

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Kiseleva I.V., Krutikova E.V., Rekstin A.R., Kryshen K.L., Rudenko L.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies