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Low viral doses are sufficient to infect cottontail rabbits with avian influenza A virus

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Abstract

Influenza A viruses (IAVs) have been reported in wild lagomorphs in environments where they share resources with waterfowl. Recent studies have conclusively shown that a North American lagomorph, cottontail rabbits (Sylvilagus sp.), become infected following exposure to IAVs and can shed significant quantities of virus. However, the minimum infectious dose and the efficiency of various routes of infection have not been evaluated. Thirty-six cottontail rabbits were used in a dose response study assessing both the oral and nasal routes of infection. The nasal route of infection proved to be the most efficient, as all cottontail rabbits shed viral RNA following inoculation with doses as low as 102 EID50. The oral route of infection was less efficient, but still produced infection rates of ≥ 50% at relatively low doses (i.e., 103 and 104 EID50). These results suggest that cottontail rabbits are highly susceptible to IAVs at low exposure doses that have been routinely observed in environments contaminated by waterfowl. Furthermore, this study supports earlier observations that cottontail rabbits may pose a biosecurity risk to poultry operations, as a virus-contaminated water source or contaminated environment, even at low viral titers, could be sufficient to initiate viral replication in cottontail rabbits.

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References

  1. Achenbach JE, Bowen RA (2011) Transmission of avian influenza A viruses among species in an artificial barnyard. PLoS One 6:e17643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Armstrong DM, Fitzgerald JP, Meaney CA (2011) Mammals of Colorado, 2nd edn. University Press of Colorado, Boulder

    Google Scholar 

  3. Bentler KT, Gossett DN, Root JJ (2012) A novel isoflurane anesthesia induction system for raccoons. Wildl Soc Bull 36:807–812

    Article  Google Scholar 

  4. Bulaga LL, Garber L, Senne DA, Myers TJ, Good R, Wainwright S, Trock S, Suarez DL (2003) Epidemiologic and surveillance studies on avian influenza in live-bird markets in New York and New Jersey, 2001. Avian Dis 47:996–1001

    Article  CAS  PubMed  Google Scholar 

  5. Cui P, Hou Y, Xing Z, He Y, Li T, Guo S, Luo Z, Yan B, Yin Z, Lei F (2011) Bird migration and risk for H5N1 transmission into Qinghai Lake, China. Vector Borne Zoonotic Dis 11:567–576

    Article  PubMed  PubMed Central  Google Scholar 

  6. Guan Y, Farooqui A, Zhu H, Dong W, Wang J, Kelvin DJ (2013) H7N9 Incident, immune status, the elderly and a warning of an influenza pandemic. J Infect Dev Ctries 7:302–307

    Article  PubMed  Google Scholar 

  7. Hall JS, Bentler KT, Landolt G, Elmore SA, Minnis RB, Campbell TA, Barras SC, Root JJ, Pilon J, Pabilonia K, Driscoll C, Slate D, Sullivan H, McLean RG (2008) Influenza infection in wild raccoons. Emerg Infect Dis 14:1842–1848

    Article  PubMed  PubMed Central  Google Scholar 

  8. Horimoto T, Maeda K, Murakami S, Kiso M, Iwatsuki-Horimoto K, Sashika M, Ito T, Suzuki K, Yokoyama M, Kawaoka Y (2011) Highly pathogenic avian influenza virus infection in feral raccoons, Japan. Emerg Infect Dis 17:714–717

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ip HS, Torchetti MK, Crespo R, Kohrs P, DeBruyn P, Mansfield KG, Baszler T, Badcoe L, Bodenstein B, Shearn-Bochsler V, Killian ML, Pedersen JC, Hines N, Gidlewski T, DeLiberto T, Sleeman JM (2015) Novel Eurasian highly pathogenic influenza A H5 viruses in wild birds, Washington, USA, 2014. Emerg Infect Dis 21:886–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ito T, Okazaki K, Kawaoka Y, Takada A, Webster RG, Kida H (1995) Perpetuation of influenza A viruses in Alaskan waterfowl reservoirs. Arch Virol 140:1163–1172

    Article  CAS  PubMed  Google Scholar 

  11. Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A (2011) An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. Jpn J Vet Res 59:89–100

    PubMed  Google Scholar 

  12. NVSL (2003) Avian influenza agar gel immunodiffusion test to detect serum antibodies to type A influenza viruses. NVSL document AVPRO0100.05

  13. Okuya K, Kawabata T, Nagano K, Tsukiyama-Kohara K, Kusumoto I, Takase K, Ozawa M (2015) Isolation and characterization of influenza A viruses from environmental water at an overwintering site of migratory birds in Japan. Arch Virol 160:3037–3052

    Article  CAS  PubMed  Google Scholar 

  14. Piaggio AJ, Shriner SA, VanDalen KK, Franklin AB, Anderson TD, Kolokotronis SO (2012) Molecular surveillance of low pathogenic avian influenza viruses in wild birds across the United States: inferences from the hemagglutinin gene. PLoS One 7:e50834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. ProMED-mail (2015) Avian influenza (68): USA (Minnesota, South Dakota) HPAI H5N2, Turkeys. ProMed-Mail 20150405.3277704

  16. Root JJ, Bentler KT, Shriner SA, Mooers NL, VanDalen KK, Sullivan HJ, Franklin AB (2014) Ecological routes of avian influenza virus transmission to a common mesopredator: an experimental evaluation of alternatives. PLoS One 9:e102964

    Article  PubMed  PubMed Central  Google Scholar 

  17. Root JJ, Shriner SA, Bentler KT, Gidlewski T, Mooers NL, Ellis JW, Spraker TR, VanDalen KK, Sullivan HJ, Franklin AB (2014) Extended viral shedding of a low pathogenic avian influenza virus by striped skunks (Mephitis mephitis). PLoS One 9:e70639

    Article  PubMed  PubMed Central  Google Scholar 

  18. Root JJ, Shriner SA, Bentler KT, Gidlewski T, Mooers NL, Spraker TR, VanDalen KK, Sullivan HJ, Franklin AB (2014) Shedding of a low pathogenic avian influenza virus in a common synanthropic mammal—the cottontail rabbit. PLoS One 9:e103513

    Article  Google Scholar 

  19. Root JJ, Shriner SA, Ellis JW, VanDalen KK, Sullivan HJ, Franklin AB (2015) When fur and feather occur together: interclass transmission of avian influenza A virus from mammals to birds through common resources. Sci Rep 5:12354

    Article  Google Scholar 

  20. Root JJ, Bosco-Lauth AM, Bielefeldt-Ohmann H, Bowen RA (2016) Experimental infection of peridomestic mammals with emergent H7N9 (A/Anhui/1/2013) influenza A virus: implications for biosecurity and wet markets. Virology 487:242–248

    Article  CAS  PubMed  Google Scholar 

  21. Shriner SA, VanDalen KK, Mooers NL, Ellis JW, Sullivan HJ, Root JJ, Franklin AB (2012) Low-pathogenic avian influenza viruses in wild house mice. PLoS One 7:e39206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Spackman E, Senne DA, Bulaga LL, Myers TJ, Perdue ML, Garber LP, Lohman K, Daum LT, Suarez DL (2003) Development of real-time RT-PCR for the detection of avian influenza virus. Avian Dis 47:1079–1082

    Article  CAS  PubMed  Google Scholar 

  23. Sullivan HJ, Blitvich BJ, VanDalen K, Bentler KT, Franklin AB, Root JJ (2009) Evaluation of an epitope-blocking enzyme-linked immunosorbent assay for the detection of antibodies to influenza A virus in domestic and wild avian and mammalian species. J Virol Methods 161:141–146

    Article  CAS  PubMed  Google Scholar 

  24. Team RDC (2010) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  25. VanDalen KK, Franklin AB, Mooers NL, Sullivan HJ, Shriner SA (2010) Shedding light on avian influenza H4N6 infection in mallards: modes of transmission and implications for surveillance. PLoS One 5:e12851

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang G, Zhan D, Li L, Lei F, Liu B, Liu D, Xiao H, Feng Y, Li J, Yang B, Yin Z, Song X, Zhu X, Cong Y, Pu J, Wang J, Liu J, Gao GF, Zhu Q (2008) H5N1 avian influenza re-emergence of Lake Qinghai: Phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation. J Gen Virol 89:697–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yee KS, Carpenter TE, Mize S, Cardona CJ (2008) The live bird market system and low-pathogenic avian influenza prevention in Southern California. Avian Dis 52:348–352

    Article  PubMed  Google Scholar 

  28. Yu Z, Cheng K, Sun W, Xin Y, Cai J, Ma R, Zhao Q, Li L, Huang J, Sang X, Li X, Zhang K, Wang T, Qin C, Qian J, Gao Y, Xia X (2014) Lowly pathogenic avian influenza (H9N2) infection in Plateau pika (Ochotona curzoniae), Qinghai Lake, China. Vet Microbiol 173:132–135

    Article  PubMed  Google Scholar 

  29. Zhou J, Sun W, Wang J, Guo J, Yin W, Wu N, Li L, Yan Y, Liao M, Huang Y, Luo K, Jiang X, Chen H (2009) Characterization of the H5N1 highly pathogenic avian influenza virus derived from wild pikas in China. J Virol 83:8957–8964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the National Wildlife Research Center (NWRC) animal care staff for excellent assistance. The opinions and conclusions of this article are those of the authors and do necessarily represent those of the U.S. Department of Agriculture. The mention of commercial products herein is for identification purposes only and does not constitute endorsement or censure.

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Correspondence to J. Jeffrey Root.

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This research was supported by the U.S. Department of Agriculture.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Root, J.J., Shriner, S.A., Ellis, J.W. et al. Low viral doses are sufficient to infect cottontail rabbits with avian influenza A virus. Arch Virol 162, 3381–3388 (2017). https://doi.org/10.1007/s00705-017-3493-z

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  • DOI: https://doi.org/10.1007/s00705-017-3493-z

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