ABSTRACT
Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Because free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity-related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced 11 candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena. Suitable single nucleotide polymorphism markers of potential functional importance, located in genes coding for basigin (BSG, CD147), the signaling lymphocyte activating molecule (SLAMF1), the poliovirus-related receptor-4 (NECTIN4, PVRL4), toll-like receptors 3, 7, 8 (TLR3, TLR7, TLR8), natural resistance-associated macrophage protein (SLC11A1) and natural cytotoxicity triggering receptor 1 (NCR1), were identified in each model species, along with MHC-DQB haplotypes unique for each species. This set of molecular markers represents a potentially useful tool for studying host genetic variation and susceptibility to morbillivirus infection in Cetaceans as well as for studying functionally important genetic diversity of selected Cetacean populations.
Subject(s)
Genetic Predisposition to Disease , Morbillivirus Infections/genetics , Morbillivirus/immunology , Phocoena/genetics , Polymorphism, Single Nucleotide , Stenella/genetics , Animals , Basigin/genetics , Basigin/immunology , Biomarkers/metabolism , Cation Transport Proteins/genetics , Cation Transport Proteins/immunology , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/immunology , Gene Expression , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Morbillivirus/pathogenicity , Morbillivirus Infections/immunology , Morbillivirus Infections/virology , Natural Cytotoxicity Triggering Receptor 1/genetics , Natural Cytotoxicity Triggering Receptor 1/immunology , Phocoena/immunology , Phocoena/virology , Signaling Lymphocytic Activation Molecule Family Member 1/genetics , Signaling Lymphocytic Activation Molecule Family Member 1/immunology , Stenella/immunology , Stenella/virology , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/immunology , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/immunology , Toll-Like Receptor 8/genetics , Toll-Like Receptor 8/immunologyABSTRACT
Individual variation in immune responses to herpesviruses was observed in various species. Here, associations between polymorphic molecular markers and life-long anti-EHV-1/4 antibody immune responses were analyzed in a model EHV-infected population of the Old Kladruber horses. Two-dimensional analysis including overall mean titers and titer dynamics expressed by differences between spring and autumn titers allowed identification of low-responders. 50 randomly selected microsatellites and nine single nucleotide polymorphisms in nine immunity-related candidate genes were genotyped. Due to differences (p<0.001) in antibody titers between two color varieties of Old Kladruber horses, separate association studies were performed in the two sub-populations by using the Fisher's exact test. In black horses, the interleukin 4 receptor and MxA protein coding genes, and the microsatellite TKY325 were associated with the responder status. In the grey population, the microsatellite TKY343 showed significant association with anti-EHV antibody responsiveness after Bonferroni corrections.
