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Genetic variation at chemokine receptor CCR5 in leporids: alteration at the 2nd extracellular domain by gene conversion with CCR2 in Oryctolagus, but not in Sylvilagus and Lepus species

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Abstract

Whereas in its natural host (Sylvilagus sps.) the effects of myxoma virus infections are benign, in European rabbit (Oryctolagus cuniculus), it causes a highly infectious disease with very high mortality rate, known as myxomatosis. There is evidence that, as with HIV-1 virus in human, myxoma virus may use chemokine receptors such as CCR5 of the host target cell for entry and activation of pathways of immune avoidance. We have characterized and compared CCR5 genes of leporid species with different susceptibility levels to myxomatosis. The CCR5 protein of O. cuniculus differs markedly from all those known from other species. The most striking was the replacement of a specific peptide motif of the second extracellular loop (ECL2) by a motif, which in other species characterizes the CCR2 molecules. While absent in Sylvilagus and Lepus species, this CCR2 imposed CCR5–ECL2 alteration was observed in all genomes of 25 European rabbits, representing the subspecies O. cuniculus algirus and O. cuniculus cuniculus. Allelic variation at the rabbit CCR5 locus confirmed that the gene conversion predates the subspecies split (1–2 Ma).

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Acknowledgements

We thank James Harris for editorial help. This work was supported by a Foundation for Science and Technology-Portugal project (POCI/BIA-BDE/61553/2004), by a grant of the Foundation for Science and Technology-Portugal (Praxis XXI/BPD/14551/2003) to P.E. and by a grant of the Belgian Fonds voor Wetenschappelijk Onderzoek Vlaanderen (Krediet 1.5579.98-FWOKN35) to W.vdL.

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Authors and Affiliations

  1. Centro de Investigação em Biodiversidade e Recursos Genéticos (CIBIO), ICETA-UP, Campus Agrário de Vairão Rua Padre Armando Quintas, Vairão, 4485-661, Portugal

    P. J. Esteves, N. Ferrand & W. van der Loo

  2. Departamento de Zoologia e Antropologia-, Faculdade de Ciências da Universidade do Porto, Porto, Portugal

    C. R. Carmo, P. J. Esteves, N. Ferrand & W. van der Loo

  3. Institute of Molecular Biology and Biotechnology, Vrije Universiteit Brussel, Brussels, Belgium

    W. van der Loo

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  1. C. R. Carmo
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  2. P. J. Esteves
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  3. N. Ferrand
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  4. W. van der Loo
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Correspondence to W. van der Loo.

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Carmo, C.R., Esteves, P.J., Ferrand, N. et al. Genetic variation at chemokine receptor CCR5 in leporids: alteration at the 2nd extracellular domain by gene conversion with CCR2 in Oryctolagus, but not in Sylvilagus and Lepus species. Immunogenetics 58, 494–501 (2006). https://doi.org/10.1007/s00251-006-0095-4

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