Potential of polylactic-co-glycolic acid (PLGA) for delivery Jembrana disease DNA vaccine Model (pEGFP-C1-tat).

BACKGROUND: The development of a vaccine for Jembrana disease is needed to prevent losses in Indonesia's Bali cattle industry. A DNA vaccine model (pEGFP-C1-tat) that requires a functional delivery system will be developed. Polylactic-co-glycolic acid (PLGA) may have potential as a delivery system for the vaccine model. OBJECTIVES: This study aims to evaluate the in vitro potential of PLGA as a delivery system for pEGFP-C1-tat. METHODS: Consensus and codon optimization for the tat gene was completed using a bioinformatic method, and the product was inserted into a pEGFP-C1 vector. Cloning of the pEGFP-C1-tat was successfully performed, and polymerase chain reaction (PCR) and restriction analysis confirmed DNA isolation. PLGA-pEGFP-C1-tat solutions were prepared for encapsulated formulation testing, physicochemical characterization, stability testing with DNase I, and cytotoxicity testing. The PLGA-pEGFP-C1-tat solutions were transfected in HeLa cells, and gene expression was observed by fluorescent microscopy and real-time PCR. RESULTS: The successful acquisition of transformant bacteria was confirmed by PCR. The PLGA:DNA:polyvinyl alcohol ratio formulation with optimal encapsulation was 4%:0.5%:2%, physicochemical characterization of PLGA revealed a polydispersity index value of 0.246, a particle size of 925 nm, and a zeta potential value of -2.31 mV. PLGA succeeded in protecting pEGFP-C1-tat from enzymatic degradation, and the percentage viability from the cytotoxicity test of PLGA-pEGFP-C1-tat was 98.03%. The PLGA-pEGFP-C1-tat demonstrated luminescence of the EGFP-tat fusion protein and mRNA transcription was detected. CONCLUSIONS: PLGA has good potential as a delivery system for pEGFP-C1-tat.

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

Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV), referred to as small ruminant lentiviruses (SRLVs), belong to the genus Lentivirus of the Retroviridae family. SRLVs infect both sheep and goats, causing significant economic losses and animal welfare damage. Recent findings suggest an association between serological status and allelic variants of different genes such as TMEM154, TLR9, MYD88 and CCR5. The aim of this work was to investigate the role of specific polymorphisms of these genes in SRLVs infection in some sheep flocks in Italy. In addition to those already known, novel variants in the TMEM154 (P7H, I74V, I105V) gene were detected in this study. The risk of infection was determined finding an association between the serological status and polymorphisms P7H, E35K, N70I, I74V, I105V of TMEM154, R447Q, A462S and G520R in TLR9 gene, H176H* and K190K* in MYD88 genes, while no statistical association was observed for the 4-bp deletion of the CCR5 gene. Since no vaccines or treatments have been developed, a genetically based approach could be an innovative strategy to prevent and to control SRLVs infection. Our findings are an important starting point in order to define the genetic resistance profile towards SRLVs infection.

Bases para um programa de controle da artrite encefalite caprina em rebanho leiteiro / [Bases for a program of control of caprine arthritis encephalite in dairy flock]

Objetivou-se avaliar um programa de controle da artrite encefalite caprina (AEC), por meio de testes diagnósticos sensíveis, separação de mãe e cria após o parto e medidas de manejo, com o intuito de formar rebanho livre do vírus. Utilizou-se um total de 47 cabritos da raça Saanen, mantidos isoladamente até o resultado dos primeiros testes de reação em cadeia de polimerase nested (PCR nested) e Western Blotting (WB), com base na coleta de sangue no momento do nascimento (M0). No PCR nested, quatro animais foram positivos, no M0, e foram eutanasiados. Posteriormente, os demais 43 cabritos foram submetidos à coleta de sangue aos 60 (M60) e 270 (M270) dias de vida para realização de novos testes de WB e PCR nested, que não detectaram animais positivos. Pode-se afirmar que a metodologia adotada neste estudo foi efetiva no controle da doença, nas fases de aleitamento e pós-aleitamento, e que a combinação do sistema de manejo, a fim de propiciar diminuição de risco de transmissão horizontal, com técnicas de diagnóstico mais apuradas, como o WB e a PCR nested, é relevante para elaboração de plano estratégico de controle da enfermidade.(AU)

We aimed to evaluate a program to control Caprine Arthritis Encephalitis (CAE), using diagnostic tests, separation of the mother and postpartum and other management measures, in order to form a free flock of the virus. We used a total of 47 Saanengoats in isolation until the results of the first nested Polymerase Chain Reaction (nested PCR) and Western Blotting (WB) tests, based on blood collection at the time of birth (M0). In the nested PCR, 4 animals were positive, at M0, and were eliminated. Later, the other 43goats were submitted to blood collection at 60 (M60) and 270 (M270) days of life to perform new tests of WB and nested PCR, which did not detect positive animals. We can affirm that the methodology adopted in this study was effective in the control of the disease, in the phase of breastfeeding and post-breastfeeding, and that the combination of the management system, which allows a reduction of risk of horizontal transmission, with more accurate diagnostic techniques, such as WB and nested PCR, is relevant for the elaboration of a strategic plan for the disease control.(AU)

Eradication of caprine arthritis encephalitis virus in the goat population of South Tyrol, Italy: analysis of the tailing phenomenon during the 2016-2017 campaign.

Since 2007, the Autonomous Province of Bolzano-South Tyrol (Italy) has carried out a compulsory eradication program against caprine arthritis encephalitis virus (CAEV) in goats. A drastic seroprevalence reduction was achieved during the initial phase (2007-2011); however, a tailing phenomenon has been observed during the latest years, hampering the achievement of the final goal. CAEV belongs to a group of lentiviruses, called small ruminant lentiviruses (SRLVs), which are antigenically related and can infect both goats and sheep. We investigated the possible link between the tailing phenomenon in goats and the role of sheep as a virus reservoir by comparing serologic results between multispecies farms (where goats and sheep coexist) and monospecies farms (goats only). Goats on multispecies farms had a higher prevalence and seroconversion rate (even if to a rather moderate extent), higher antibody titers, and a higher probability of conclusive results in the genotyping analysis, with more frequent identification of SRLV genotype A (sheep-related) infections. Sheep can serve as a SRLV reservoir, thus contributing to scattered positive tests in goats, causing the tailing phenomenon.

Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission.

Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the ß2 subunit of AP-2 to a ß hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission.

Diagnostic response to a cross-border challenge for the Swiss caprine arthritis encephalitis virus eradication program.

INTRODUCTION: Animal trading between countries with different small ruminant lentivirus infectious status is a potential danger for the reintroduction of eradicated genotypes. This was the case in 2017 with the importation of a large flock of seropositive goats into Switzerland. The handling of this case permitted us to test the preventive measures in place. The coordination between the local veterinarian and the cantonal and federal veterinary authorities worked efficiently and rapidly involved the national reference center in the investigations. This case posed a challenge for the reference center and enabled scrutiny of the applied diagnostic tests. ELISA and western blot provided consistent results and pointed to an unusually high infection rate in the flock. This was confirmed by the isolation of several viruses from different organs and cells, demonstrating that the spleen is particularly well suited for isolation of small ruminant lentiviruses. The SU5-ELISA, designed to predict the subtype of the infecting virus, correctly pointed to a B1 subtype as the infectious agent. We confirmed that with this test it is necessary to analyze a representative number of samples from a flock and not just individual sera to obtain reliable results. This analysis permitted us to identify particular amino acid residues in the SU5 peptides that may be crucial in determining the subtype specificity of antibody binding. Different gag-pol and env regions were amplified by PCR using primers designed for this purpose. The phylogenetic analysis revealed a surprisingly high heterogeneity of the sequences, pointing to multiple infections within single animals and the entire flock. In conclusion, this case showed that the defense of the CAEV negative status of the Swiss goat population with respect to the virulent, prototypic B1 subtype of small ruminant lentiviruses, requires, among other measures, a diagnostic facility capable of performing a thorough analysis of the collected samples.

INTRODUCTION: Le commerce d'animaux entre pays où le statut infectieux des lentivirus des petits ruminants est différent constitue un danger potentiel pour la réintroduction de génotypes éradiqués. Ce fut le cas en 2017 avec l'importation d'un grand troupeau de chèvres séropositives en Suisse. Le traitement de cette affaire nous a permis de tester les mesures préventives mises en place. La coordination entre le vétérinaire local et les autorités vétérinaires cantonales et fédérales a été efficace et a impliqué rapidement le centre de référence national dans les enquêtes. Ce cas a constitué un défi pour le centre de référence et a permis d'examiner de près les tests de diagnostic appliqués. Les tests ELISA et Western blot ont fourni des résultats cohérents et ont mis en évidence un taux d'infection anormalement élevé dans le troupeau. Cela a été confirmé par l'isolement de plusieurs virus provenant d'organes et de cellules différents, démontrant que la rate est particulièrement bien adaptée à l'isolement des lentivirus des petits ruminants. Le SU5-ELISA, conçu pour prédire le sous-type du virus infectant, désignait correctement un sous-type B1 en tant qu'agent infectieux. Nous avons confirmé qu'avec ce test, il était nécessaire d'analyser un nombre représentatif d'échantillons d'un troupeau et pas seulement des sérums individuels pour obtenir des résultats fiables. Cette analyse nous a permis d'identifier des résidus d'acides aminés particuliers dans les peptides SU5 qui pourraient jouer un rôle crucial dans la détermination de la spécificité de sous-type de la liaison à l'anticorps. Différentes régions gag-pol et env ont été amplifiées par PCR en utilisant des amorces conçues à cet effet. L'analyse phylogénétique a révélé une hétérogénéité étonnamment élevée des séquences, indiquant de multiples infections chez les animaux isolés et dans l'ensemble du troupeau. En conclusion, cette affaire a montré que la défense du statut négatif CAEV de la population de chèvres suisses vis-à-vis du virus virulent, sous-type B1 des lentivirus des petits ruminants, nécessite, entre autres mesures, un système de diagnostic capable d'effectuer une analyse approfondie des échantillons collectés.

Small ruminant lentiviruses in goats in southern Italy: Serological evidence, risk factors and implementation of control programs.

Small ruminant lentiviruses (SRLVs) can drastically affect milk production in goat flocks and only an early detection can control and prevent their spread. Since SRLVs are responsible for persistent infections, antibody screening is the most valuable tool to identify infected animals. ELISA is recommended as the election test both for its sensitivity and for its ability to detect low antibody titers, thus identifying infected animals earlier than agar gel immunodiffusion (AGID). In the present study, an investigation was conducted to assess the SRLV seroprevalence in goat flocks in southern Italy and a transversal comparative study was carried out through the analysis of the possible risk factors influencing SRLV spread. A total of 4800 sera from 1060 flocks were analyzed and overall seroprevalences of 18,64% and 51,69% at animal and herd levels, respectively, were observed. Both the region and the herd production systems were able to affect seroprevalence, differently from the herd size, probably because the mean number of goats per herd is low and the semi-intensive management is similar regardless of the dimensional class of each herd. In particular, meat producing herds showed the higher seroprevalence, as a result of the poor sanitation and low animal monitoring in comparison to milk producing herds, where animals are managed twice daily and the relationship between dams and kids is checked to guarantee an adequate quantitative/qualitative milk yield. In the absence of vaccines or effective treatments, health preventive management and seroepidemiological investigations are the only successful approach to restrict SRLV spread as observed in countries were official/voluntary control programs are carried out.

Achievements of an eradication programme against caprine arthritis encephalitis virus in South Tyrol, Italy.

Small ruminant lentivirus infections in goats affect both production and animal welfare. This represents a threat to the qualitative and quantitative growth of goat farming, recently observed in mountainous regions such as the Autonomous Province of Bolzano - South Tyrol (Italy). To monitor and eradicate the caprine arthritis encephalitis virus in this goat population, a compulsory eradication campaign was launched, based on a strict census of small ruminants and yearly serological testing of all animals, followed by the consequent culling of seropositive individuals. The campaign succeeded in completely eliminating cases of clinical disease in goats, while drastically reducing the seroprevalence at the herd as well as individual animal level. The serological outcome of the introduced control measures was determined using commercially available ELISA kits, demonstrating their suitability for use in this type of campaign, aimed at reducing seroprevalence as well as clinical manifestations of these infections. However, this clear success is diminished by the failure to achieve a complete eradication of these viruses. The reasons leading to the observed tailing phenomenon and the occurrence of new infections in already sanitised flocks are discussed and implementation of further measures are proposed.

Welfare effects of a disease eradication programme for dairy goats.

The Norwegian dairy goat industry has largely succeeded in controlling caprine arthritis encephalitis (CAE), caseous lymphadenitis (CLA) and paratuberculosis through a voluntary disease eradication programme called Healthier Goats (HG). The aim of this study was to apply an on-farm welfare assessment protocol to assess the effects of HG on goat welfare. A total of 30 dairy goat farms were visited, of which 15 had completed disease eradication and 15 had not yet started. Three trained observers assessed the welfare on 10 farms each. The welfare assessment protocol comprised both resource-based and animal-based welfare measures, including a preliminary version of qualitative behavioural assessments with five prefixed terms. A total of 20 goats in each herd were randomly selected for observations of human-animal interactions and physical health. The latter included registering abnormalities of eyes, nostrils, ears, skin, lymph nodes, joints, udder, claws and body condition score. For individual-level data, robust clustered logistic regression analyses with farm as cluster variable were conducted to assess the association with disease eradication. Wilcoxon rank-sum tests were used for comparisons of herd-level data between the two groups. Goats with swollen joints (indicative of CAE) and enlarged lymph nodes (indicative of CLA) were registered on 53% and 93% of the non-HG farms, respectively, but on none of the HG farms. The only other health variables with significantly lower levels in HG herds were skin lesions (P=0.008) and damaged ears due to torn out ear tags (P<0.001). Goats on HG farms showed less fear of unknown humans (P=0.013), and the qualitative behavioural assessments indicated that the animals in these herds were calmer than in non-HG herds. Significantly more space and lower gas concentrations reflected the upgrading of buildings usually done on HG farms. In conclusion, HG has resulted in some welfare improvements beyond the elimination of infectious diseases. The protocol was considered a useful tool to evaluate the welfare consequences of a disease eradication programme. However, larger sample sizes would increase the reliability of prevalence estimates for less common conditions and increase the power to detect differences between the groups. Despite the obvious link between disease and suffering, this aspect is rarely taken into account in the evaluation of disease control programmes. We therefore propose that welfare assessment protocols should be applied to evaluate the merits of disease control or eradication programmes in terms of animal welfare.

Small ruminant lentivirus infections and diseases.

Small ruminant lentiviruses include viruses with diverse genotypes that frequently cross the species barrier between sheep and goats and that display a great genetic variability. These characteristics stress the need to consider the whole host range and to perform local surveillance of the viruses to opt for optimum diagnostic tests, in order to establish control programmes. In the absence of effective vaccines, a comprehensive knowledge of the epidemiology of these infections is of major importance to limit their spread. This article intends to cover these aspects and to summarise information related to characteristics of the viruses, pathogenesis of the infection and description of the various syndromes produced, as well as the diagnostic tools available, the mechanisms involved in transmission of the pathogens and, finally, the control strategies that have been designed until now, with remarks on the drawbacks and the advantages of each one. We conclude that there are many variables influencing the expected cost and benefits of control programs that must be evaluated, in order to put into practice measures that might lead to control of these infections.

Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.

Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

Pharmacokinetic evaluation of tenofovir disoproxil fumarate released from an intravaginal ring in pigtailed macaques after 6 months of continuous use.

BACKGROUND AND METHODS: A reservoir intravaginal ring (IVR) eluting tenofovir disoproxil fumarate (TDF) was evaluated for 6 months of continuous use in normally cycling female pigtailed macaques with monthly IVR exchanges to define pharmacokinetics and safety. RESULTS AND CONCLUSIONS: Tenofovir levels in vaginal secretions and tissue remained consistent for 6 months with no adverse safety concerns.

Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques.

It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti-HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (∼1:100) and potentially achievable by vaccination.

The Norwegian Healthier Goats program--modeling lactation curves using a multilevel cubic spline regression model.

In 2001, the Norwegian Goat Health Service initiated the Healthier Goats program (HG), with the aim of eradicating caprine arthritis encephalitis, caseous lymphadenitis, and Johne's disease (caprine paratuberculosis) in Norwegian goat herds. The aim of the present study was to explore how control and eradication of the above-mentioned diseases by enrolling in HG affected milk yield by comparison with herds not enrolled in HG. Lactation curves were modeled using a multilevel cubic spline regression model where farm, goat, and lactation were included as random effect parameters. The data material contained 135,446 registrations of daily milk yield from 28,829 lactations in 43 herds. The multilevel cubic spline regression model was applied to 4 categories of data: enrolled early, control early, enrolled late, and control late. For enrolled herds, the early and late notations refer to the situation before and after enrolling in HG; for nonenrolled herds (controls), they refer to development over time, independent of HG. Total milk yield increased in the enrolled herds after eradication: the total milk yields in the fourth lactation were 634.2 and 873.3 kg in enrolled early and enrolled late herds, respectively, and 613.2 and 701.4 kg in the control early and control late herds, respectively. Day of peak yield differed between enrolled and control herds. The day of peak yield came on d 6 of lactation for the control early category for parities 2, 3, and 4, indicating an inability of the goats to further increase their milk yield from the initial level. For enrolled herds, on the other hand, peak yield came between d 49 and 56, indicating a gradual increase in milk yield after kidding. Our results indicate that enrollment in the HG disease eradication program improved the milk yield of dairy goats considerably, and that the multilevel cubic spline regression was a suitable model for exploring effects of disease control and eradication on milk yield.

A first-in-class NAE inhibitor, MLN4924, blocks lentiviral infection in myeloid cells by disrupting neddylation-dependent Vpx-mediated SAMHD1 degradation.

MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells. SAMHD1 is required for MLN4924-mediated SIVmac inhibition. Our findings indicate the potential efficacy of inhibiting neddylation as an antiretroviral strategy and identify the readily available anticancer drug MLN4924 as a candidate agent for that purpose.

High-throughput profiling of anti-glycan humoral responses to SIV vaccination and challenge.

Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.

Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges.

Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 10(5) ng/mL (range 1.1 × 10(4) to 6.6 × 10(5) ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans.

Immunization against small ruminant lentiviruses.

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.

Expanding possibilities for intervention against small ruminant lentiviruses through genetic marker-assisted selective breeding.

Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions.