Candidate gene molecular markers as tools for analyzing genetic susceptibility to morbillivirus infection in stranded Cetaceans

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.

Deiminated proteins and extracellular vesicles as novel biomarkers in pinnipeds: Grey seal (Halichoerus gryptus) and harbour seal (Phoca vitulina)

“…Roles for MHC class I can also serve as an inhibitory ligand for natural killer cells and this mechanism can be exploited by viruses, which can inhibit various stages of the MHC class I antigen presentation pathway for immune evasion [71][72][73] as well as by some cancer cells, which can downregulate MHC I to avoid normal immune surveillance [74][75]. MHC I has been studied in harbour seal [76], with possible variation suggested in immune response genes in relation to susceptibility to phocine distemper virus [77] and with respect to morbillivirus infection in stranded cetaceans [78].…”

Whole genomes reveal multiple candidate genes and pathways involved in the immune response of dolphins to a highly infectious virus

“…At least 29 genes have been proposed to potentially play a role in immune responses to morbilliviruses in general (Hashiguchi et al, 2011; Haralambieva et al, 2015; McCarthy et al, 2011; Stejskalova et al, 2017), but only three of these ( PATJ , MAPK8 and IL4α ) were found to be under putative selection between cases and controls in this study. For the remaining 26 genes, 22 aligned to the SABD reference genome.…”

“…At least 29 genes have been proposed to potentially play a role in immune responses to morbilliviruses in general (Hashiguchi et al, 2011;Haralambieva et al, 2015;McCarthy et al, 2011;Stejskalova et al, 2017), but only three of these (PATJ, MAPK8 and IL4α) were found to or enhancer regions of the genes. The majority of the 22 genes were highly polymorphic (Table S7); however, inspection of genotype counts for the top performing SNP within each gene (i.e., SNP with greatest allele frequency differences between cases and controls) highlighted a lack of heterozygosity within 11 of the immune genes across all samples (Figure 3, Table S7).…”

“…For example, the signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for measles, canine distemper, rinderpest and peste des petitis ruminants viruses, and is suggested to be a universal receptor for entry and propagation of morbillivirus in all mammals, including cetaceans (Melia et al, 2014; Ohishi et al, 2019; Sato et al, 2012; Shimizu et al, 2013). Other genes, including viral binding genes, cytokine receptor genes, pathogen‐associated sensing genes and antiviral genes were also suggested to be involved in immune responses to morbilliviruses (Hashiguchi et al, 2011; McCarthy et al, 2011; Haralambieva et al, 2015; Stejskalova et al, 2017).…”

Marine Morbilliviruses: Diversity and Interaction with Signaling Lymphocyte Activation Molecules

“…Natural infection of seals with CeMV; however, has rarely been documented. This suggests that host factors other than SLAMs are involved in the host–virus specificity of morbilliviruses [175,176]. In addition, ecological factors that facilitate contact of host animals may be a key factor in determining morbillivirus host specificity.…”