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Oxidative stress in wild European rabbits naturally infected with myxoma virus and rabbit haemorrhagic disease virus

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Abstract

The European rabbit (Oryctolagus cuniculus) is one of the most important vertebrate species in the Mediterranean Basin ecosystem. Over the last 60 years, the arrival of two viral diseases, myxomatosis and rabbit haemorrhagic disease, have led to dramatic declines in wild rabbit populations across the Iberian Peninsula. These diseases are currently endemic. Periodic outbreaks occur and have significant impacts on wild populations. Both infection types have diverse physiological effects on their hosts that are rooted in aerobic metabolic processes. To fight off these viruses, rabbits activate their immune systems. However, the production of immune defences generates reactive oxygen species that may consequently damage host tissues. Hypothesising that immune responses increase oxidative stress, we examined whether wild rabbits naturally infected with myxoma virus (MV) and rabbit haemorrhagic disease virus (RHDV) had high oxidative stress. Using blood samples, we measured anti-MV and anti-RHDV antibody concentrations and different oxidative stress markers (i.e., glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and malondialdehyde). Our results show that rabbits that were seropositive for both MV and RHDV had high concentrations of malondialdehyde. Age and body condition were also positively related to dual seropositivity. No significant relationships were observed between serostatus and the concentrations of the other oxidative stress markers. Although we expected infection with MV and RHDV to be correlated with oxidative stress, the influence of external sources of oxidative stress (e.g., climatic conditions) likely made it more difficult to detect such relationships in wild rabbits.

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Abbreviations

ROS:

Reactive oxygen species

OS:

Oxidative stress

AOX:

Antioxidant

MV:

Myxoma virus

RHD:

Rabbit haemorrhagic disease

RHDV:

Rabbit haemorrhagic disease virus

GPX:

Glutathione peroxidase

GR:

Glutathione reductase

SOD:

Superoxide dismutase

CAT:

Catalase

MDA:

Malondialdehyde

References

  • Alves P, Moreno S (1996) Estudo da reprodução do coelho-bravo (Oryctolagus cuniculus) em Portugal. Rev Florestal 9:149–166

    Google Scholar 

  • Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399

    Article  PubMed  CAS  Google Scholar 

  • Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581

    Article  PubMed  CAS  Google Scholar 

  • Bertó-Moran A, Pacios I, Serrano E, Moreno S, Rouco C (2013) Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits. J Wildl Dis 49:10–17

    Article  PubMed  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  PubMed  CAS  Google Scholar 

  • Calvete C, Estrada R, Villafuerte R, Osácar JJ, Lucientes J (2002) Epidemiology of viral haemorrhagic disease and myxomatosis in a free-living population of wild rabbits. Vet Rec 150:776–781

    Article  PubMed  CAS  Google Scholar 

  • Cameron CM, Barrett JW, Liu L, Lucas AR, McFadden G (2005a) Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down-regulation of macrophage and T-cell activation in vivo. J Virol 79:6052–6067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cameron CM, Barrett JW, Mann M, Lucas A, McFadden G (2005b) Myxoma virus M128L is expressed as a cell surface CD47-like virulence factor that contributes to the downregulation of macrophage activation in vivo. Virology 337:55–67

    Article  PubMed  CAS  Google Scholar 

  • Carmagnol F, Sinet PM, Jerome H (1983) Selenium-dependent and non-selenium-dependent glutathione peroxidases in human tissue extracts. Biochim Biophys Acta 759:49–57

    Article  PubMed  CAS  Google Scholar 

  • Christensen LL, Selman C, Blount JD, Pilkington JG, Watt KA, Pemberton JM, Reid JM, Nussey DH (2015) Plasma markers of oxidative stress are uncorrelated in a wild mammal. Ecol Evol 5:5096–5108

    Article  PubMed  PubMed Central  Google Scholar 

  • Clarkson PM, Thompson HS (2000) Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr 72:637s–646s

    Article  PubMed  CAS  Google Scholar 

  • Cohen AA, McGraw KJ (2009) No simple measures for antioxidant status in birds: complexity in inter-and intraspecific correlations among circulating antioxidant types. Funct Ecol 23:310–320

    Article  Google Scholar 

  • Cohen G, Somerson NL (1969) Glucose-dependent secretion and destruction of hydrogen peroxide by mycoplasma pneumoniae. J Bacteriol 98:547–551

    PubMed  PubMed Central  CAS  Google Scholar 

  • Costantini D (2008) Oxidative stress in ecology and evolution: lessons from avian studies. Ecol Lett 11:1238–1251

    Article  PubMed  Google Scholar 

  • Costantini D, Dell’Omo G, De Filippis PS, Marquez C, Snell H, Snell H, Tapia W, Brambilla G, Gentile G, (2009) Temporal and spatial covariation of gender and oxidative stress in the Galápagos land iguana Conolophus subcristatus. Physiol Biochem Zool 82:430–437

  • Costantini D (2014) Oxidative stress and hormesis in evolutionary ecology and physiology. A marriage between mechanistic and evolutionary approaches. Springer, Berlin

    Google Scholar 

  • Costantini D, Møller AP (2009) Does immune response cause oxidative stress in birds? A meta-analysis. Comp Biochem Physiol A 153:339–344

    Article  CAS  Google Scholar 

  • Costantini D, Verhulst S (2009) Does high antioxidant capacity indicate low oxidative stress? Funct Ecol 23:506–509

    Article  Google Scholar 

  • Cribb AE, Leeder JS, Spielberg SP (1989) Use of a microplate reader in an assay of glutathione reductase using 5, 50-dithiobis (2-nitrobenzoic acid). Anal Biochem 183:195–196

    Article  PubMed  CAS  Google Scholar 

  • Dowling DK, Simmons LW (2009) Reactive oxygen species as universal constraints in life-history evolution. Proc R Soc Lond B Biol Sci 276:1737–1745

    Article  CAS  Google Scholar 

  • Evans GO (2008) Animal hematotoxicology: a practical guide for toxicologists and biomedical researchers. CRC Press

  • Foyer CH, Noctor G (2005) Oxidant and antioxidant signalling in plants: a re-evaluation of the concept of oxidative stress in a physiological context. Plant Cell Environ 28:1056–1071

    Article  CAS  Google Scholar 

  • García-Bocanegra I, Astorga RJ, Napp S, Casal J, Huerta B, Borge C, Arenas A (2010) Myxomatosis in wild rabbit: design of control programs in Mediterranean ecosystems. Prev Vet Med 93:42–50

    Article  PubMed  Google Scholar 

  • Gassó D, Vicente J, Mentaberre G, Soriguer R, Rodríguez RJ, Navarro-González N, Tvarijonaviciute A, Lavín S, Fernández-Llario P, Segalés J, Serrano E (2016) Oxidative stress in wild boars naturally and experimentally infected with Mycobacterium bovis. PLoS One 11:e0163971

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gechev TS, Van Breusegem F, Stone JM, Denev I, Laloi C (2006) Reactive oxygen species as signals that modulate plant stress responses and programmed cell death. BioEssays 28:1091–1101

    Article  PubMed  CAS  Google Scholar 

  • Gibbs HL, Chiucchi JE (2012) Inbreeding, body condition, and heterozygosity-fitness correlations in isolated populations of the endangered eastern massasauga rattlesnake (Sistrurus c. Catenatus). Conserv Genet 13:1133–1143

    Article  Google Scholar 

  • Halliwell B, Gutteridge JMC (1999) The chemistry of free radicals and related ‘reactive species’. Free Radic Biol Med 3:1–7

    Google Scholar 

  • Halliwell BH, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

    Google Scholar 

  • Harman E (1956) Protein oxidation in aging and age-related diseases. Gerontology 11:298–300

    Article  CAS  Google Scholar 

  • Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 87:1175–1213

    Article  PubMed  CAS  Google Scholar 

  • Johnston JB, Barrett JW, Chang W, Chung C-S, Zeng W, Masters J, Mann M, Wang F, Cao J, McFadden G (2003) Role of the serine-threonine kinase PAK-1 in myxoma virus replication. J Virol 77:5877–5888

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kerr PJ (2012) Myxomatosis in Australia and Europe: a model for emerging infectious diseases. Antivir Res 93:387–415

    Article  PubMed  CAS  Google Scholar 

  • Kerr PJ, McFadden G (2002) Immune responses to myxoma virus. Viral Immunol 15:229–246

    Article  PubMed  CAS  Google Scholar 

  • Lastra RG (2009) Mecanismos moleculares implicados en la fisiopatología de la enfermedad hemorrágica del conejo, un modelo animal de fallo hepático fulminante. Doctoral dissertation, Universidad de León

  • Legendre P (2008) lmodel2: Model II Regression. R package version 1.6–3

  • Lochmiller RL, Deerenberg C (2000) Trade-offs in evolutionary immunology: just what is the cost of immunity? Oikos 88:87–98

    Article  Google Scholar 

  • Maceda-Veiga A, Figuerola J, Martínez-Silvestre A, Viscor G, Ferrari N, Pacheco M (2015) Inside the Redbox: applications of haematology in wildlife monitoring and ecosystem health assessment. Sci Total Environ 514:322–332

    Article  PubMed  CAS  Google Scholar 

  • Marri V, Richner H (2015) Immune response, oxidative stress and dietary antioxidants in great tit nestlings. Comp Biochem Physiol A 179:192–196

    Article  CAS  Google Scholar 

  • Masters J, Hinek AA, Uddin S, Platanias LC, Zeng W, McFadden G, Fish EN (2001) Poxvirus infection rapidly activates tyrosine kinase signal transduction. J Biol Chem 276:48371–48375

    Article  PubMed  CAS  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    PubMed  CAS  Google Scholar 

  • Monaghan P, Metcalfe NB, Torres R (2009) Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett 12:75–92

    Article  PubMed  Google Scholar 

  • Norte AC, Ramos JA, Sousa JP, Sheldon BC (2009) Variation of adult great tit Parus major body condition and blood parameters in relation to sex, age, year and season. J Ornithol 150:651–660

    Article  Google Scholar 

  • Nussey DH, Pemberton JM, Pilkington JG, Blount JD (2009) Life history correlates of oxidative damage in a free-living mammal population. Funct Ecol 23:809–817

    Article  Google Scholar 

  • Pacios-Palma I, Santoro S, Bertó-Moran A, Moreno S, Rouco C (2016) Effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological condition of wild European rabbits: is blood biochemistry a useful monitoring tool? Res Vet Sci 109:129–134

    Article  PubMed  Google Scholar 

  • Pap PL, Sesarman A, Vágási CI, Buehler DM, Pătraş L, Versteegh MA, Banciu M (2014) No evidence for parasitism-linked changes in immune function or oxidative physiology over the annual cycle of an avian species. Physiol Biochem Zool 87:729–739

    Article  PubMed  Google Scholar 

  • Peig J, Green AJ (2009) New perspectives for estimating body condition from mass/length data: the scaled mass index as an alternative method. Oikos 118:1883–1891

    Article  Google Scholar 

  • Prior RL, Cao G (1999) In vivo total antioxidant capacity: comparison of different analytical methods 1. Free Radic Biol Med 27:1173–1181

    Article  PubMed  CAS  Google Scholar 

  • R Core Team (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URL https://www.R-project.org/

    Google Scholar 

  • Raja-aho S, Kanerva M, Eeva T, Lehikoinen E, Suorsa P, Gao K, Vosloo D, Nikinmaa M (2012) Seasonal variation in the regulation of redox state and some biotransformation enzyme activities in the barn swallow (Hirundo rustica L.). Physiol Biochem Zool 85:148–158

    Article  PubMed  CAS  Google Scholar 

  • Rouco C, Ferreras P, Castro F, Villafuerte R (2008) The effect of exclusion of terrestrial predators on short-term survival of translocated European wild rabbits. Wildl Res 35:625–632

    Article  Google Scholar 

  • Rouco C, Villafuerte R, Castro F, Ferreras P (2011) Effect of artificial warren size on a restocked European wild rabbit population. Anim Conserv 14:117–123

    Article  Google Scholar 

  • Rubolini D, Colombo G, Ambrosini R, Caprioli M, Clerici M, Colombo R, Dalle-Donne I, Milzani A, Romano A, Romano M, Saino N (2012) Sex-related effects of reproduction on biomarkers of oxidative damage in free-living barn swallows (Hirundo rustica). PLoS One 7:e48955

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sanchez-Campos S, Alvarez M, Culebras JM, Gonzalez-Gallego J, Tunon MJ (2004) Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease. J Lab Clin Med 144:215–222

    Article  PubMed  CAS  Google Scholar 

  • Schneeberger K, Czirják GÁ, Voigt CC (2013) Inflammatory challenge increases measures of oxidative stress in a free-ranging, long-lived mammal. J Exp Biol 216:4514–4519

    Article  PubMed  CAS  Google Scholar 

  • Selman C, Blount JD, Nussey DH, Speakman JR (2012) Oxidative damage, ageing, and life-history evolution: where now? Trends Ecol Evol 27:570–577

    Article  PubMed  Google Scholar 

  • Sies H (1991) Oxidative stress: from basic research to clinical application. Am J Med 91:S31–S38

    Article  Google Scholar 

  • Sorci G, Faivre B (2009) Inflammation and oxidative stress in vertebrate host-parasite systems. Philos Trans R Soc B 364:71–83

    Article  Google Scholar 

  • Tanchev S, Gadjeva V, Stanilova S (2003) Influence of antigen stimulation on the oxidative stress parameters in outbred and inbred rabbits. Arch Physiol Biochem 111:437–442

    Article  PubMed  CAS  Google Scholar 

  • Tunon MJ, Sanchez-Campos S, Garcia-Ferreras J, Alvarez M, Jorquera F, Gonzalez-Gallego J (2003) Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure. J Lab Clin Med 141:272–278

    Article  PubMed  Google Scholar 

  • Vallejo D, Crespo I, San-Miguel B, Álvarez M, Prieto J, Tuñón MJ, González-Gallego J (2014) Autophagic response in the rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure. Vet Res 45:15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van de Crommenacker J, Horrocks NP, Versteegh MA, Komdeur J, Tieleman BI, Matson KD (2010) Effects of immune supplementation and immune challenge on oxidative status and physiology in a model bird: implications for ecologists. J Exp Biol 213:3527–3535

    Article  PubMed  CAS  Google Scholar 

  • Villafuerte R (1994) Riesgo de predación y estrategias defensivas del conejo en el Parque Nacional de Doñana. Doctoral dissertation. Universidad de Córdoba

  • Villafuerte R, Castro F, Ramírez E, Cotilla I, Parra F, Delibes-Mateos M, Recuerda P, Rouco C (2017) Large-scale assessment of myxomatosis prevalence in European wild rabbits (Oryctolagus cuniculus) 60 years after first outbreak in Spain. Res Vet Sci 114:281–286

    Article  PubMed  Google Scholar 

  • von Schantz T, Bensch S, Grahn M, Hasselquist D, Wittzell H (2016) Good genes, oxidative stress and condition-dependent sexual signals. Proc R Soc Lond Ser B Biol Sci 266:1–12

    Article  Google Scholar 

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Acknowledgements

Isabel Pacios Palma was supported by a predoctoral Severo Ochoa grant from the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Program for Centers of Excellence in R+D+I (SEV-2012-0262). Carlos Rouco was funded by XXII Propio de Investigación of the University of Córdoba and “Programa Operativo de fondos FEDER Andalucía”. Special thanks to J. Pearce (www.englishservicesforscientists.com) for her language editing services and to Dr. Alberto Maceda-Veiga and Laura Rios Pena for their helpful comments, which improved the manuscript. Finally, thanks to V. Morlanes, C. Marfil, G. Macías, and A. Bertó for their assistance in the field.

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Correspondence to Isabel Pacios-Palma.

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All animal experimentation was carried out in accordance with Spanish and European regulations (Law 32/2007, Council Directive 2010/63/EU, R.D. 53/2013, ECC/566/2015).

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Pacios-Palma, I., Moreno, S., Selman, C. et al. Oxidative stress in wild European rabbits naturally infected with myxoma virus and rabbit haemorrhagic disease virus. Eur J Wildl Res 64, 47 (2018). https://doi.org/10.1007/s10344-018-1203-0

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  • DOI: https://doi.org/10.1007/s10344-018-1203-0

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