A single nucleotide variant in the promoter region of the CCR5 gene increases susceptibility to arthritis encephalitis virus in goats

Abstract

Background The small ruminant lentiviruses (SRLVs) are a heterogeneous group of viruses that includes caprine arthritis encephalitis virus (CAEV) and Maedi-Visna virus (MVV). SRLVs affect the production and welfare of sheep and goats worldwide. There is currently no effective treatment. Their high mutation rate precludes vaccine development, making innovative control measures necessary. A variant of the chemokine (C-C motif) receptor 5 (CCR5) gene is reportedly involved in resistance to human immunodeficiency (HIV) infection in humans and to SRLV in sheep. The aim of this study was to analyse the genetic structure and variability of the CCR5 gene in goats and to carry out a cross-sectional study to investigate the role of CCR5 genetic variants in controlling susceptibility/resistance to CAEV. Results The variant g.1059 T located in the promoter region revealed an interesting association with high proviral loads (a 2.8-fold increased risk). A possible explanation could be an alteration of the transcriptional level. Overexpression of the CCR5 receptor on the cell surface may increase virus internalization and proviral load as a consequence. Conclusions Our findings could be advantageously used to reduce the susceptibility of goat herds to CAEV by negatively selecting animals carrying the g.1059 T mutation. Eliminating animals predisposed to high proviral loads could also limit the development of clinical signs and the spread of the virus, since these animals are also highly efficient in shedding the virus. Electronic supplementary material The online version of this article (10.1186/s12917-019-1979-5) contains supplementary material, which is available to authorized users.

First Survey of SNPs in TMEM154, TLR9, MYD88 and CCR5 Genes in Sheep Reared in Italy and Their Association with Resistance to SRLVs Infection

“…The investigation of genes involved in resistance/susceptibility to SRLVs infection has been conducted by several authors in order to identify SNPs as markers to be used as an alternative approach to control the infection, ensuring animal welfare and reducing the significant economic losses in infected flocks [ 5 ]. However, in Italy, few data on the frequencies of genetic variants are available and only regarding goat flocks in Northern and Southern Italy [ 26 , 37 , 38 ].…”

“…Since SRLVs are macrophage-tropic lentiviruses likewise HIV, a number of flocks was analyzed to assess if the deletion in the CCR5 gene could exist, eventually contributing to the resistance to SRLVs infection [ 11 , 20 , 26 ]. Actually, a CCR5 four base pairs deletion, ( CCR5 -Δ4-rs119102753) was associated to a lower proviral load of SRLVs together with a lower CCR5 gene expression [ 20 ].…”

Transcriptome Analysis for Genes Associated with Small Ruminant Lentiviruses Infection in Goats of Carpathian Breed

“…Several attempts to identify host factors associated with resistance to SRLV infections have been made, and some loci were identified [11][12][13][14][15]. In particular TMEM154 gene (transmembrane protein 154), TMEM38A (transmembrane protein 38A), CCR5 (chemokine(C-C motif) receptor type 5), MHC (major histocompatibility complex), ZNF389 (zinc-finger protein 389), TLRs (toll-like receptors), APOBEC3 (apolipoprotein B editing complex 3), TRIM5 (tripartite motif protein 5 alpha), Tetherin/BST-2 (bone marrow stromal cell antigen 2) and other cytokines (interleukin 2 (IL2), interleukin 2 receptor (IL2R), tumor necrosis factor alfa (TNF-α), interleukin 4 (IL4), interleukin 8 (IL8), interleukin 6 (IL6), interleukin 16 (IL-16), interferon gamma (IFN-γ), transforming growth factor beta (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF)) and chemokine ligands (C-C motif ligand 2 (CCL2), C-C motif ligand 5 (CCL5), C-C motif ligand 20 (CCL20)) seem to have an important role in the SRLV infection susceptibility/resistance [12,13,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. However, additional studies are still necessary to learn more about genes involved in SRLV immunity.…”

Short communication: Genetic parameter estimates for caprine arthritis encephalitis in dairy goats

“…Genetic selection for CAE-resistant goats could play a major role in improving welfare and increasing industry profitability by reducing CAE prevalence in herds. Even though disease susceptibility has been mainly affected by environmental factors, genetic variation can also contribute to the level of infection resistance (Brito et al, 2018;Colussi et al, 2019). In this context, the main objective of this study was to estimate variance components and genetic parameters for CAE resistance using Bayesian threshold models, which consider the binary nature of the trait.…”