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Simple Summary: Small ruminant lentiviruses (SRLVs) are responsible for a disease complex that includes a variety of clinical forms with a large degree of severity. The virus is highly variable, and 5 genotypes with 34 subgenotypes have been described so far. However, the application of different protocols for genotyping generated contradictory results with potential misclassification of some strains and/or identification of redundant new subgenotypes. To the best of our knowledge, no systematic review on the molecular characterization of SRLVs in sheep and goats is available. The present systematic review aims to provide an updated, in-depth, comprehensive overview of the phylogenesis of SRLVs. The systematic review was developed according to the PRISMA-P statement. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Maedi-visna is a globally distributed, viral, and incurable chronic disease of small ruminants, challenging the health and welfare of sheep and jeopardizing the sustainability of farms. Currently, the scarcity of representative, updated, and epidemiological data hinders the implementation of successful eradication programs. The objective of our study is to prospectively study the seroepidemiology of maedi-visna in intensively reared dairy sheep. For this reason, a total of 407 purebred Chios and Lacaune ewes from four farms were studied for two successive years, and blood samples were semiannually collected and tested using the ELISA test. Prevalence and incidence rates were found to have increased in all the studied farms, highlighting the importance of horizontal transmission of the virus within the farms. Various serological patterns were observed in the studied animals, namely, constantly seronegative, constantly seropositive, seroconverted, seroreverted, or animals with an intermittent presence of antibodies. The last two categories indicate a special immune response of infected animals which needs to be further investigated and considered for the diagnosis of MV and when designing eradication programs. The objective of this study is to prospectively evaluate the seroepidemiology of maedi-visna (MV) infections in intensively reared dairy sheep. A total of 407 purebred Chios and Lacaune ewes from four farms were surveyed for two consecutive years and were serologically tested semiannually with an indirect ELISA at pre-mating and pre-lambing. The farms' structure and management practices were similar and animal traits (age, breed, and production stage) were recorded. Based on the serological status, morbidity frequency measures were estimated, and ewes were categorized as constantly seronegative, constantly seropositive, seroconverted, seroreverted, or as animals with an intermittent presence of antibodies. During the study, period seroprevalence, incidence rate, and cumulative incidence were 84.8%, 33.6 new cases per 100 sheep-semesters, and 64.2%. Point-seroprevalence ranged from 48.5% to 96.0% among the studied farms and sampling occasions, and they increased by age. Increased morbidity frequency measures indicate the significance of horizontal transmission in intensive dairy sheep farms. A remarkable percentage of infected animals seroreverted (8.1%) or presented an intermittent presence of antibodies (10.3%) during the study, confirming the risk of misdiagnosis in cross-sectional studies and in the currently implemented testing and elimination programs. The serological patterns observed in our study need to be considered when studying MV epidemiology and for the designing of efficient MV elimination programs. [ABSTRACT FROM AUTHOR]

Small ruminant lentiviruses (SRLVs) affect sheep and goats worldwide. The major gene related to SRLV infections is the Transmembrane Protein Gene 154 (TMEM154). We estimated the haplotype frequencies of TMEM154 in the USA (USDA-ARS) and Brazil (Embrapa) Gene Banks by using two different SNP genotyping methodologies, FluidigmTM and KASPTM. We also genotyped the ZNF389_ss748775100 deletion variant in Brazilian flocks. A total of 1040 blood samples and 112 semen samples from 15 Brazilian breeds were genotyped with Fluidigm for the SNP ZNF389_ss748775100 and 12 TMEM154 SNPs. A total of 484 blood samples from the Santa Inês breed and 188 semen samples from 14 North American sheep breeds were genotyped with KASP for 6 TMEM154 SNPs. All the Brazilian samples had the "I/I" genotype for the ZNF389_ss748775100 mutation. There were 25 TMEM154 haplotypes distributed across the Brazilian breeds, and 4 haplotypes in the US breeds. Haplotypes associated with susceptibility were present in almost all breeds, which suggests that genetic testing can help to improve herd health and productivity by selecting non-susceptible animals as founders of the next generations. Fluidigm and KASP are reliable assays when compared with Beadchip arrays. Further studies are necessary to understand the unknown role of TMEM154 mutations, host–pathogen interaction and new genes associated with the clinical condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Local breeds represent a precious reservoir of genetic diversity, crucial to adapting to environmental and climate changes and reacting to evolving diseases. In Sicily, four native dairy breeds, namely Valle del Belìce, Comisana, Barbaresca, and Pinzirita, have adapted to low-input farming systems and semiarid environments, having an essential role in producing high-quality milk and typical dairy products. Maedi-visna (MV) is one of the most important chronic diseases affecting the sheep sector worldwide, causing production losses. Different target genes play an important role in immunity and in genetic resilience to MV, such as TMEM154, TLR9, MYD88, and CCR5. A major host genetic component to sheep MV susceptibility was identified in the ovine TMEM154 gene. Animals with either of TMEM154 haplotypes that encode glutamate at position 35 (E35) of the protein are at higher risk of MV infection than those homozygous with lysine at position 35 (K35). In the tested Sicilian breeds, animals carrying the allele E35 showed a greater risk of being serologically positive. Comisana, Barbaresca, and Pinzirita breeds showed a good frequency of the protective allele K35, whilst a high frequency of risk allele was found in the Valle del Belìce breed, related to the selection strategies addressed to obtain a productive dairy sheep. Our results highlight the importance of the preservation of autochthonous breeds as a reservoir of natural resistance against infectious disease. Maedi-visna (MV) is a disease caused by small ruminant lentiviruses. It is included in the list of notifiable terrestrial animal diseases due to economic losses and animal welfare harm in the sheep sector. To date, control programs remain the onliest approach to avoiding infection. The allelic variant p.Glu35Lys (E35K) of the TMEM154 gene has been strongly associated with host vulnerability to MV illness. The present study aimed to investigate the association of TMEM154 E35K allele frequencies with MV susceptibility in native Sicilian sheep breeds. More than 400 animals from 14 local sheep were serologically tested and genotyped for the TMEM154 E35K polymorphism. The local breeds displayed different values of MV seroprevalence, with the lowest antibody prevalence in Barbaresca and Pinzirita breeds. TMEM154 protective allele (K35) was less frequent than the risk allele (E35) in Valle del Belìce breed, whereas the other three breeds showed a more balanced alleles distribution. A positive association between seroprevalence and genotype was found in the entire sample set. The risk of infection resulted in more than 3-fold times as high in sheep with EK and EE genotype compared to the KK genotype. Our data could be helpful in establishing selection breeding programs aimed at reducing MV infection in Sicilian sheep farming and encouraging the breeding of native breeds. [ABSTRACT FROM AUTHOR]

The results of previous studies of SRLV infections in wild ruminants suggest that wild ruminants may serve as virus reservoirs responsible for the infections of domestic small ruminants. It is possible that SRLVs circulate in free-ranging mouflons in Slovenia, but considering the results of previous studies in which SRLV infections were detected in mouflons, it is very likely that the detected seropositive animal is an accidental spillover host for SRLV. Keywords: small ruminant lentiviruses; SRLV; maedi-visna; caprine arthritis-encephalitis; chamois; mouflon; serology; ELISA; survey EN small ruminant lentiviruses SRLV maedi-visna caprine arthritis-encephalitis chamois mouflon serology ELISA survey N.PAG N.PAG 6 04/26/22 20220415 NES 220415 1. [Extracted from the article]

Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV) in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease. [ABSTRACT FROM AUTHOR]

Small ruminant lentiviruses (SRLVs), i.e., CAEV and MVV, cause insidious infections with life-long persistence and a slowly progressive disease, impairing both animal welfare and productivity in affected herds. The complex diagnosis of SRLVs currently combines serological methods including whole-virus and peptide-based ELISAs and Immunoblot. To improve the current diagnostic protocol, we analyzed 290 sera of animals originating from different European countries in parallel with three commercial screening ELISAs, Immunoblot as a confirmatory assay and five SU5 peptide ELISAs for genotype differentiation. A newly developed nested real-time PCR was carried out for the detection and genotype differentiation of the virus. Using a heat-map display of the combined results, the drawbacks of the current techniques were graphically visualized and quantified. The immunoblot and the SU5-ELISAs exhibited either unsatisfactory sensitivity or insufficient reliability in the differentiation of the causative viral genotype, respectively. The new truth standard was the concordance of the results of two out of three screening ELISAs and the PCR results for serologically false negative samples along with genotype differentiation. Whole-virus antigen-based ELISA showed the highest sensitivity (92.2%) and specificity (98.9%) among the screening tests, whereas PCR exhibited a sensitivity of 75%. [ABSTRACT FROM AUTHOR]

Small ruminant lentiviruses (SRLVs) infections lead to chronic diseases and remarkable economic losses undermining health and welfare of animals and the sustainability of farms. Early and definite diagnosis of SRLVs infections is the cornerstone for any control and eradication efforts; however, a "gold standard" test and/or diagnostic protocols with extensive applicability have yet to be developed. The main challenges preventing the development of a universally accepted diagnostic tool with sufficient sensitivity, specificity, and accuracy to be integrated in SRLVs control programs are the genetic variability of SRLVs associated with mutations, recombination, and cross-species transmission and the peculiarities of small ruminants' humoral immune response regarding late seroconversion, as well as intermittent and epitope-specific antibody production. The objectives of this review paper were to summarize the available serological and molecular assays for the diagnosis of SRLVs, to highlight their diagnostic performance emphasizing on advantages and drawbacks of their application, and to discuss current and future perspectives, challenges, limitations and impacts regarding the development of reliable and efficient tools for the diagnosis of SRLVs infections. [ABSTRACT FROM AUTHOR]

Simple Summary: Maedi-visna is a progressive wasting disease of sheep that leads to decreased animal condition and production. It is caused by Small Ruminant Lentiviruses (SRLV), single-stranded RNA viruses with high mutational potential. There is neither treatment nor vaccine against SRLV and proper diagnosis is the key element for efficient control measures against positive animals. This systematic review and meta-analysis summarizes the individual and flock prevalence of SRLV throughout the world and describes the diagnostic tests employed over the last four decades. Our results indicate that Europe is the continent with the most information on the prevalence of the infection as well as with the highest SRLV prevalence at the individual level. Flock prevalence depends directly on the individual prevalence. SRLV diagnostic methods in sheep have substantially changed during the last decades, but serologic methods have always been the most frequently used techniques for prevalence studies. A combination of at least two diagnostic tests is fully encouraged for future prevalence studies and health programs. ELISA and PCR show synergic effects in SRLV diagnosis. Small Ruminant Lentiviruses (SRLV) are highly prevalent retroviruses with significant genetic diversity and antigenic heterogeneity that cause a progressive wasting disease of sheep called Maedi-visna. This work provides a systematic review and meta-analysis of the last 40 years (1981–2020) of scientific publications on SRLV individual and flock prevalence. Fifty-eight publications and 314 studies were included. Most articles used a single diagnostic test to estimate prevalence (77.6%), whereas articles using three or more tests were scarce (6.9%). Serological tests are more frequently used than direct methods and ELISA has progressively replaced AGID over the last decades. SRLV infection in sheep is widespread across the world, with Europe showing the highest individual prevalence (40.9%) and being the geographical area in which most studies have been performed. Africa, Asia, and North America show values between 16.7% to 21.8% at the individual level. South and Central America show the lowest individual SRLV prevalence (1.7%). There was a strong positive correlation between individual and flock prevalence (ρ = 0.728; p ≤ 0.001). Despite the global importance of small ruminants, the coverage of knowledge on SRLV prevalence is patchy and inconsistent. There is a lack of a gold standard method and a defined sampling strategy among countries and continents. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no data on the effect of the transmembrane protein 154 (TMEM154) E35K variants on susceptibility to small ruminant lentivirus (SRLV) infection in Iranian sheep breeds, and only limited data for German sheep flocks. This study aimed at investigating the association of TMEM154 variants and SRLV infection status in Iranian and German sheep flocks and breeds. Three out of the four analyzed sheep flocks/breeds showed a significant association between TMEM154 variants and SRLV prevalence. A complementary analysis was carried out based on regression analysis to test the relationship between frequency of the TMEM154 E allele and SRLV prevalence in different flocks/breeds. Results showed that the TMEM154 E allele frequencies could be useful for predicting genetic susceptibility to SRLV infection in a sheep flock or breed. Finally, the genetic susceptibility of different Iranian and German sheep breeds was compared based on the frequency of the TMEM154 E allele. 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. [ABSTRACT FROM AUTHOR]