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Small ruminant lentiviruses (SRLVs) are responsible for chronic and progressive multisystemic clinical forms, which significantly reduce flocks' productivity and have a considerable economic impact on the small ruminant industry. Due to the increase in genetic analysis studies and the potential for misclassification of certain strains, owing to the high genetic variability of these viruses, a systematic review was deemed necessary. This review explores the types of matrices used for molecular detection and phylogenetic studies, the genomic regions selected as targets, and the software utilized for phylogenetic analysis, assessing the geographical distribution of identified genotypes and subgenotypes over time. A thorough comparison of the diagnostic approaches highlights the strengths and limitations of each method, identifying gaps that need to be addressed. Additionally, recombination events and compartmentalization are examined to provide an updated, detailed, and comprehensive overview of SRLV phylogenesis.

The Maedi-visna virus (MVV) causes a persistent infection in small ruminants, and its high genetic heterogeneity affects the performance of diagnostic tests when used in different populations. Therefore, the aim of this study was to develop a bead-based multiplex immunoassay tailored to detect antibodies against a Norwegian MVV strain. We used tissue samples from 14 PCR-positive sheep from a recent MVV outbreak in Norway to sequence the viral strain and produced recombinant antigens based on sequences from one animal. The assay included commercial TM-A and recombinant Norwegian p25, p16-25 and SU5 antigens. Cut-off values for each antigen were determined using receiver operating characteristic curves on 40 ELISA-negative and 67 ELISA-positive samples from the outbreak. The intraplate and interplate repeatability were investigated by testing a quadruplicate of five samples over three days, while the analytical sensitivity (aSe) and specificity (aSp) were measured in comparison to a commercial ELISA. The repeatability showed a coefficient of variation below 15% for most positive samples. The aSe was equal or higher for the multiplex assay than the ELISA, and the aSp of each antigen was 91.7, 93.3, 95.0 and 93.3% for p25, p16-25, SU5 and TM-A, respectively. The assay shows promising results; however, further evaluations of diagnostic characteristics are necessary before implementation in the Norwegian surveillance programme.

Small ruminant lentivirus (SRLV) causes Maedi-Visna or Ovine Progressive Pneumonia in sheep and creates insidious livestock production losses. This retrovirus is closely related to human immunodeficiency virus and currently has no vaccines or cure. Genetic marker assisted selection for sheep disease resiliency presents an attractive management solution. Previously, we identified a region containing a cluster of zinc finger genes that had association with ovine SRLV proviral concentration. Trait-association analysis validated a small insertion/deletion variant near ZNF389 (rs397514112) in multiple sheep breeds. In the current study, 543 sheep from two distinct populations were genotyped at 34 additional variants for fine mapping of the regulatory elements within this locus. Variants were selected based on ChIP-seq annotation data from sheep alveolar macrophages that defined active cis-regulatory elements predicted to influence zinc finger gene expression. We present a haplotype block of variants within regulatory elements that have improved associations and larger effect sizes (up to 4.7-fold genotypic difference in proviral concentration) than the previously validated ZNF389 deletion marker. Hypotheses for the underlying causal mutation or mutations are presented based on changes to in silico transcription factor binding sites. These variants offer alternative markers for selective breeding and are targets for future functional mutation assays.

The immune response to a viral antigen causes inflammatory cell infiltration to the tissue, which creates a suitable environment for the replication of the virus in macrophages, and the recruitment of more monocytes to the site of infection, or latently infected monocytes. The aim of the study was to analyze the transcriptomic profile of peripheral blood nuclear cells isolated from SRLV-seropositive and SRLV-negative goats at the peak of their first lactation. SRLV-seropositive goats were probably infected via colostrum. Custom transcriptomic microarrays for goats were designed and developed, namely the Capra hircus gene expression array, which features ~50,000 unique transcripts per microarray. Only four genes were differentially expressed, with up-regulated expression of the GIMAP2, SSC5D and SETX genes, and down-regulated expression of the GPR37 gene in SRLV-seropositive vs. SRLV-seronegative goats. However, in an RT-qPCR analysis, the result for the SETX gene was not confirmed. The differences in the expressions of the studied genes indicate an active inflammatory process in the SRLV-seropositive goats at the early stage of infection.

Maedi-visna (MV) in sheep is caused by maedi-visna virus (MVV), a small ruminant lentivirus (SRLV) that causes chronic infection and inflammatory lesions in infected animals. Pneumonia and mastitis are its predominant clinical manifestations, and the tissues infected by MVV are mainly the lungs, the mammary gland, the nervous system and the joints. MV has a worldwide distribution with distinct MVV transmission patterns depending on circulating strains and regionally applied control/eradication schemes. Nevertheless, the prevalence rate of MV universally increases. Currently, gaps in understanding the epizootiology of MV, the continuous mutation of existing and the emergence of new small ruminant lentiviruses (SRLVs) strains, lack of an effective detection protocol and the inefficiency of currently applied preventive measures render elimination of MV an unrealistic target. Therefore, modifications on the existing MV surveillance and control schemes on an evidentiary basis are necessary. Updated control schemes require the development of diagnostic protocols for the early and definitive diagnosis of MVV infections. The objectives of this review are to summarize the current knowledge in the epizootiology and control of MV in dairy sheep, to describe the research framework and to cover existing gaps in understanding future challenges regarding MV.

Small ruminant lentiviruses (SRLVs) cause maedi-visna disease in sheep and are prevalent in Iran and Germany. The association of the transmembrane protein 154 (TMEM154) variants with SRLV infection has been previously identified by a genome-wide association (GWAS) approach and subsequent analyses, and validated in some US, German, and Turkish sheep flocks. We aimed at evaluating these findings for the first time in Iranian, and in some more German sheep flocks/breeds. Also, we aimed at comparing the SRLV susceptibility in Iranian and German sheep based on the frequency of the TMEM154 E35 allele. About 800 blood samples were collected from 21 Iranian and German sheep flocks/breeds for different purposes: (1) The association of TMEM154 E35K with SRLV infection status was tested in four sheep breeds and found to be significant in Kermani, Merinoland, and Brown Hair. (2) The usefulness of the TMEM154 E35 frequency for predicting SRLV susceptibility was evaluated by regression analysis, combining data from this study and some already published data. Results showed a significant association between E35 frequency and SRLV prevalence. (3) SRLV susceptibility was compared based on E35 frequency in Iranian and German sheep. Altogether, findings of this study provide valuable information on SRLV susceptibility, using TMEM154 E35, in Iranian and German sheep.