MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi–Visna and pulmonary adenocarcinoma viral diseases in sheep

Abstract

Ovine pulmonary adenocarcinoma (OPA) and Maedi-Visna (Maedi) are two chronic respiratory diseases of retroviral origin which occur worldwide. It is known that different host genetic factors influence the outcome of viral infections. To determine if variation in the Mhc-DRB1 gene was associated with progression to these ovine diseases, sheep lungs with and without OPA and Maedi lesions were collected. A sequence-based method was applied and 40 different alleles were detected in the sample analysed. In the allele-by-allele association analysis, allele DRB1*0325 had a significant association with susceptibility to Maedi (P = 0.045). For OPA, DRB1*0143 and DRB1*0323 were significantly associated with susceptibility (P = 0.024 and P = 0.029), and allele DRB1*0702 was significantly associated with resistance (P = 0.012). Based on these results, the Mhc-DRB1 alleles were classified by effect in three categories-susceptible (S), resistant (R) and neutral (N)-and animals were reassigned the genotypes as S/S, S/R, S/N, R/R, R/N and N/N. In a second analysis, penalised logistic regression models including a flock effect were run. In Maedi, significant association was detected for the N/S heterozygote (P = 0.0007), but not for the S/S homozygote, probably as a result of the low number of S/S animals. In OPA, association was detected for both the S/S and R/R homozygotes (P = 0.005 and P = 0.047). This allele grouping method may be applied in association studies with highly variable genes. This is the first study demonstrating significant associations between sheep Mhc-DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are suitable candidates for more comprehensive genetic studies.

Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

“…Ovine gene regions including CCR5 and DRB1 were previously associated with OPP provirus levels in candidate gene studies [41], [42], [43]. However, the OvineSNP50 BeadChip marker density and distribution were not sufficient for evaluating whether CCR5 and DRB1 gene regions were associated with OPPV infection in the present study.…”

“…Moreover, an infected person receiving transplanted stem cells lacking CCR5 may be cured of HIV [39]. In the cases of VMV and OPPV, reports have suggested that host resistance to lentiviral infection may also occur in sheep [40], [41], [42], [43]. Significant breed effects on seroprevalence have also been observed in comingled flocks of purebred sheep, further indicating possible host genetic restriction [10], [12].…”

SNPs in candidate genes MX dynamin‐like GTPase and chemokine (C‐C motif) receptor‐5 are associated with ovine pulmonary adenocarcinoma progression in Latxa sheep

“…Our previous work analysed the involvement of major histocompatibility complex class I and II loci in OPA and identified several alleles associated with the presence of OPA lesions (Larruskain et al 2010(Larruskain et al , 2012a. This SNPbased work extends the analysis of ovine immunity genes that could influence the pathogenesis of OPA, analysing cytokines, a chemokine receptor, Toll-like receptors (TLRs) and three other innate immunity genes with antiviral activity.…”

Diagnostic Assays Used to Control Small Ruminant Lentiviruses

“…3,45 In the MHC class II Ovar-DRB1 study, 41 DRB1*07012 and DRB1*0403 alleles were significantly associated with ovine progressive pneumonia provirus loads 10-fold and 2.5-fold lower, respectively, in the blood of 405 Columbia, Polypay, and Rambouillet sheep in the United States. Another more recent study, 51 in 165 Laxta sheep of Spain, suggested that DRB1*0353 was significantly associated with lung lesions consistent with VISNA. In the CCR5 study, 80 a homozygous deletion in an octamer transcription element site in the promoter of CCR5 was significantly associated with ovine progressive pneumonia provirus loads in the blood that were 2.5-fold lower.…”