title: An overview of the lagomorph immune system and its genetic diversity.
abstract: Our knowledge of the lagomorph immune system remains largely based upon studies of the European rabbit (Oryctolagus cuniculus), a major model for studies of immunology. Two important and devastating viral diseases, rabbit hemorrhagic disease and myxomatosis, are affecting European rabbit populations. In this context, we discuss the genetic diversity of the European rabbit immune system and extend to available information about other lagomorphs. Regarding innate immunity, we review the most recent advances in identifying interleukins, chemokines and chemokine receptors, Toll-like receptors, antiviral proteins (RIG-I and Trim5), and the genes encoding fucosyltransferases that are utilized by rabbit hemorrhagic disease virus as a portal for invading host respiratory and gut epithelial cells. Evolutionary studies showed that several genes of innate immunity are evolving by strong natural selection. Studies of the leporid CCR5 gene revealed a very dramatic change unique in mammals at the second extracellular loop of CCR5 resulting from a gene conversion event with the paralogous CCR2. For the adaptive immune system, we review genetic diversity at the loci encoding antibody variable and constant regions, the major histocompatibility complex (RLA) and T cells. Studies of IGHV and IGKC genes expressed in leporids are two of the few examples of trans-species polymorphism observed outside of the major histocompatibility complex. In addition, we review some endogenous viruses of lagomorph genomes, the importance of the European rabbit as a model for human disease studies, and the anticipated role of next-generation sequencing in extending knowledge of lagomorph immune systems and their evolution.
authors.affiliation: InBIO-Research Network in Biodiversity and Evolutionary Biology, CIBIO, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr. 7, 4485-661, Vairão, Portugal.|Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal.|SaBio-IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13071, Ciudad Real, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pinheiro
authors.affiliation: InBIO-Research Network in Biodiversity and Evolutionary Biology, CIBIO, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr. 7, 4485-661, Vairão, Portugal.|UMIB/UP-Unidade Multidisciplinar de Investigação Biomédica, Universidade do Porto, Porto, Portugal.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Neves
authors.affiliation: Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Lemos de Matos
authors.affiliation: InBIO-Research Network in Biodiversity and Evolutionary Biology, CIBIO, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr. 7, 4485-661, Vairão, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Abrantes
authors.affiliation: InBIO-Research Network in Biodiversity and Evolutionary Biology, CIBIO, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr. 7, 4485-661, Vairão, Portugal.
authors.forename: Wessel
authors.initials: W
authors.lastname: van der Loo
authors.affiliation: NIAID, NIH, Bethesda, MD, 20892, USA.
authors.forename: Rose
authors.initials: R
authors.lastname: Mage
authors.affiliation: InBIO-Research Network in Biodiversity and Evolutionary Biology, CIBIO, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr. 7, 4485-661, Vairão, Portugal. pjesteves@cibio.up.pt.|Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal. pjesteves@cibio.up.pt.|CITS-Centro de Investigação em Tecnologias de Saúde, CESPU, Gandra, Portugal. pjesteves@cibio.up.pt.
authors.forename: Pedro José
authors.initials: PJ
authors.lastname: Esteves
mesh_terms: D000820:Animal Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D000818:Animals; D005075:Biological Evolution; D004198:Disease Susceptibility; D014644:Genetic Variation; D005828:Genetics, Population; D007107:Immune System; D007109:Immunity / Q000235:genetics / Q000276:immunology; D007793:Lagomorpha / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D010802:Phylogeny; D011817:Rabbits; D014777:Virus Diseases / Q000662:veterinary
keywords: Adaptive immunity; European rabbit; Genetic diversity; Innate immunity; Lagomorphs