A census to determine the prevalence and risk factors for caprine arthritis-encephalitis virus and visna/maedi virus in the Swiss goat population.

In Switzerland, viruses belonging to two different phylogenetic groups of small ruminant lentiviruses (SRLV) are currently circulating: the caprine arthritis-encephalitis virus (CAEV) and visna/maedi virus (VMV). In the past two decades, a mandatory national control program has led to a very low prevalence of seropositivity, while completely eliminating CAE as a clinical manifestation. However, in order to reduce the high costs and effort associated with this program, adjustments based on the most recent epidemiological knowledge are needed. The purpose of this study was to estimate the seroprevalence of CAEV and VMV using the newest diagnostic tools available, and to identify potential risk factors for infection with these viruses in Switzerland. For the prevalence estimation, a census was carried out including 10,696 farms with a total of 85,454 goats. Blood samples were analysed using a 3-step serological testing algorithm consisting of Chekit ELISA, Western Blot and SU5 ELISA. A risk factor analysis was conducted using logistic regression models built with data obtained from a mail questionnaire, and serological results from the census. The apparent herd-level prevalences were 0.38%, 2.77%, and 3.04% for CAEV, VMV and SRLV, respectively. Animal-level prevalences were 0.06% for CAEV, 0.55% for VMV, and 0.61% for SRLV. No statistically significant risk factors associated with CAEV or VMV infection were identified. However, the proportional high number of CAEV seropositive dwarf goats, in relation to their population size, could indicate that these hobby breeds may slip through some of the official controls. For an infection with SRLV, a medium herd size (7-40 goats) was found to be protective, compared with smaller (OR=1.90, p=0.034) and larger herds (OR=1.95, p=0.038). In conclusion, considering that all CAEV positive animals were culled, these results imply that CAEV is no longer actively spreading and has successfully been controlled in Switzerland. However, given the uncertain pathogenic potential of VMV in goats, future surveillance should also be taking into account the not insignificant number of VMV circulating in the Swiss goat population.

Extensive rearing hinders Maedi-Visna Virus (MVV) infection in sheep.

Maedi-Visna Virus (MVV) seroprevalence and its relationship with housing and mode of rearing of replacement ewe-lambs was investigated in 38 non-randomly selected sheep-flocks in Spain. They included extensive lamb-producing Manchega cross-bred flocks raised almost permanently at pasture, semi-intensive Latxa dairy flocks housed 2-8 months/year and intensively raised Assaf dairy flocks housed most time and at higher stocking density in less ventilated buildings than other flocks. Most flocks raised replacement lambs naturally with their dams until weaning and as a separate flock thereafter until lambing at one year of age. Seroprevalence (95% confidence intervals) was 77%, 25% and 5% (4-6) in intensive, semi-intensive and extensive flocks, respectively and the median (interquartile range) flock-seroprevalence was 82% (66-94) in intensive flocks, 31% (14-31) in semi-intensive flocks and 4% (0-7) in extensive flocks. Seroprevalence was lowest in one year-old sheep and increased to flock levels during the year after introduction into the adult flock in most intensive flocks and more gradually in other flocks. Adult flock seroprevalence was associated with housing time but this relationship was not evident within a particular rearing system, indicating that other unknown factors are critical in horizontal MVV-transmission. Low seroprevalence in extensive flocks further supports previous indications that lactogenic MVV-infection is relatively inefficient and horizontal transmission is necessary to ensure long-term maintenance of MVV and this could explain that MVV has not been reported from countries with mainly extensively reared sheep such as Australia and New Zealand. Moreover, it indicates that MVV-control in extensive and semi-intensive flocks can be simple and inexpensive.

Establishment of a maedi-visna-free flock after the purchase of infected sheep.

Maedi-visna (MV) infection was detected in a cohort of 68 purchased ewes, one of several groups of sheep introduced to a farm after the previous stock had been culled with suspected foot-and-mouth disease in 2001. Except for short periods totalling six to seven weeks when the sheep co-grazed with 13 ewe lambs and ram lambs, the infected cohort was kept separate from other sheep on the farm over a total of 21 months. During this period two crops of lambs were reared from the infected ewes. All the lambs were fattened and killed, and all ewes were culled after the second crop of lambs had been weaned. Subsequent serological testing of the remaining sheep on the farm confirmed the elimination of MV infection from the flock, leading to its acceptance in the Maedi Visna Accreditation Scheme of the Scottish Agricultural College's Sheep and Goat Health Schemes.

Oxidant-antioxidant imbalance in the experimental interstitial lung disease induced in sheep by visna-maedi virus.

Infection of sheep by visna-maedi virus causes an interstitial pneumonitis similar to that associated with human immunodeficiency virus type-1 (HIV-1). Visna-maedi virus infection of alveolar macrophages leads to their activation. In this study we determined whether an imbalance in oxidant-antioxidant activity may be involved in the pathogenesis of the disease. We investigated the spontaneous and phorbol myristate acetate (PMA)-induced release of hydrogen peroxide (H2O2), and the activities of superoxide dismutase and glutathione peroxidase in alveolar macrophages from lambs experimentally-infected with visna-maedi virus, and in ovine alveolar macrophages infected in vitro. Alveolar macrophages from lambs experimentally-infected in vivo exhibited normal spontaneous H2O2 release and had superoxide dismutase and glutathione peroxidase activities similar to those from control animals. In contrast, after in vitro stimulation with PMA the H2O2 production by macrophages from experimentally-infected lambs was significantly increased. Similarly, spontaneous and PMA-induced H2O2 production by in vitro infected macrophages was significantly increased as compared to controls. In conclusion, the increased capacity of alveolar macrophages infected with the human immunodeficiency virus type-1-related visna-maedi virus to release hydrogen peroxide on stimulation suggests an oxidant-antioxidant imbalance, which may contribute to the pathogenesis of the observed chronic interstitial pneumonitis.

Increased expression of tissue factor mRNA and procoagulant activity in ovine lentivirus-infected alveolar macrophages.

To link ovine lentivirus infection to lung tissue damage, we studied the procoagulant response in alveolar macrophages from experimentally infected lambs and in in vitro infected alveolar macrophages. We cloned ovine tissue factor cDNA and analysed its in vitro expression by Northern blotting. Visna-maedi virus induced tissue factor mRNA. In order to correlate this mRNA induction with its cellular function, we analysed macrophage procoagulant activity after in vitro and in vivo infection. The procoagulant activity was increased by interaction with the virus in both cases. Thus, visna-maedi virus-induced expression of tissue factor mRNA was associated with enhanced macrophage procoagulant activity. These findings indicate an active role of alveolar macrophages in the pathogenesis of these inflammatory lung lesions.

Pathogenesis of lymphoid interstitial pneumonia in natural and experimental ovine lentivirus infection.

Ovine lentivirus (OvLV), as a member of the lentivirinae subfamily of Retroviridae, shares morphological, genomic, and cytopathic features with human immunodeficiency virus (HIV). Although OvLV infection does not induce profound immune deficiency in sheep, it has many similarities with HIV infection, such as the capacity to infect macrophages, undergo antigenic variation in vivo, and induce slow progressive diseases involving the pulmonary, lymphoid, and central nervous systems. Studies of the pathogenesis of disease in sheep naturally or experimentally infected by OvLV are providing clues to the pathogenesis of HIV infection, including the significance of viral load, the emergence of cytopathic variants, the mechanisms and significance of viral antigenic variation, and viral neutralization, and mechanisms of lymphoproliferation and tissue destruction induced by the virus. Preliminary evidence suggests that infection by other microbial agents, including Mycoplasma species, may play a cofactor role in the pathogenesis of lentivirus-associated lymphoid interstitial pneumonia in sheep, but further studies are required to address this issue.

[Interferon in sheep]. / Interferon beim Schaf.

There is only limited information on sheep interferon available. Recent publications have reported on: 1. an interferon (IFN) alpha subtype, which is secreted by the fetal trophectoderm into the lumen of the uterus between the 10th and 21st day of gestation. It was therefore named ovine trophoblast protein (oTP-1), and is responsible for signalling pregnancy to the ewe via high affinity receptors in the endometrium. It is thought that oTP-1 acts by directly influencing prostaglandin metabolism. 2. the role of lentivirus-induced interferon (LV-IFN) in the pathogenesis of Maedi/Visna. The results indicate that LV-IFN limits viral replication and therefore contributes to virus persistence and is also responsible for a chronic inflammatory process. 3. the mitogen- or antigen-dependent induction of ovine interferon gamma (IFN gamma) and its characterization.

[Diffuse interstitial pneumopathies caused by lentivirus (HIV-1) in humans and animals]. / Pneumopathies interstitielles diffuses dues aux lentivirus chez l'homme (HIV-1) et chez l'animal.

Lentiviruses belong to the retroviruses family (ie RNA viruses with reverse transcriptase activity); they induce inflammatory and/or degenerative slowly progressive diseases, affecting various organs. Some lentiviruses preferentially infect lymphocytes (HIV-1 and HIV-2, SIV and FIV) and are associated with infectious and tumoral disorders. Most lentiviruses induce a pulmonary disease, typically diffuse interstitial pneumonia. The visna/maedi-virus of sheep infects monocyte macrophage cells and the pulmonary lesions are macrophagic and neutrophilic alveolitis, lymphoid infiltration, myomatosis and interstitial fibrosis. Such pulmonary lesions are also induced by the goat and equine lentiviruses. In humans infected by HIV-1 or HIV-2, a diffuse interstitial lung disease also occurs; the histological findings are of alveolitis associated with lymphoid peribronchovascular infiltrates. The mechanism of formation of the lesions involves complex cellular interactions (especially between macrophage and lymphocyte, via cytokine production). These interactions are well modelled by small ruminant lentivirus induction of interstitial pneumonia.

Lentivirus-host interactions: lessons from visna and caprine arthritis-encephalitis viruses.

The biological properties of the ruminant animal lentiviruses, visna and caprine arthritis-encephalitis viruses, closely resemble those of their human counterparts, the human immunodeficiency viruses (HIV). All of these viruses are morphologically identical and are disseminated from host to host in nature during exchange of body fluids. Artificial conditions that favor excess exchange of such fluids precipitate epidemics by these viruses. The strategy of replication of the animal viruses in tissue culture and in vivo are very similar to that of the human virus. Virus replication is highly productive in tissue culture and leads to cytopathic effects characterized by fusion. In vivo, the rate of virus replication is restricted and lesions, suggestive of an immunopathological origin, develop after prolonged periods of subclinical infection. Similar to the animal viruses, the human viruses have a tropism for macrophages in vivo, and this leads somehow to a loss of T helper lymphocytes and proliferation of cytotoxic lymphocytes. In addition, the viruses are highly neurotropic and this results in acute fulminating disease in neonatal hosts and chronic encephalopathy in adults. Both animal and human viruses cause persistent infections and have similar strategies for eluding host immune responses. These include sequestration of neutralizing epitopes, induction of low titers of neutralizing antibodies, and antigenic drift during persistent infection. Despite close homology between genetic sequences of HIV-I and -II, these two viruses seem to have as much biological disparity from each other as does visna virus from caprine arthritis-encephalitis virus. The latter two viruses induce neutralizing antibodies that are highly strain specific and show no cross protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of visna/maedi and caprine arthritis-encephalitis: new leads on the mechanism of restricted virus replication and persistent inflammation.

Lentiviruses are unique retroviruses which cause diseases with long incubation periods and prolonged clinical courses. The prototype lentiviruses, visna/maedi of sheep and arthritis-encephalitis virus of goats (CAEV), infect cells of the monocyte-macrophage system and replicate at a restricted level in these cells. The virus life cycle is closely associated with maturational factors in the cells; monocytes support the early stages of the replication cycle which goes to completion only when the cells mature to macrophages. Virus replication in the monocyte-macrophage results in lesions characterized by mononuclear cell infiltration of the central nervous system (CNS), lungs, synovium and mammary gland and their draining lymph nodes. Co-cultivation of sheep or goat lymphocytes with macrophages infected with visna or CAE viruses results in production of a unique interferon (LV-IFN). LV-IFN is a non-glycosylated protein of 54,000 to 64,000 daltons and has biological properties which have several implications for pathogenesis. Firstly, it retards the rate of maturation of monocytes and thus indirectly slows the rate of virus replication. Second, it restricts the rate of virus replication in mature macrophages by preventing virus maturation. Third, it induces expression of class II (Ia) antigens of the major histocompatibility complex on cells of macrophage lineage. Thus, by curtailing virus replication and enhancing expression of MHC class II antigens, LV-IFN may contribute to the induction and augmentation of the host's lymphoproliferative response to the virus.

Pathogenesis of maedi-visna.

In most cases, maedi-visna virus infection is characterised by a subclinical, persistent virus-carrier state. However, in heavily infected flocks, economically significant disease does occur, mainly apparent as ill-thrift and chronic respiratory disease (maedi) in older ewes and as an indurative mastitis, which can result in delayed weight gain of suckled lambs. Meningoencephalitis (visna) and arthritis may also occur. Maedi-visna virus, a lentivirus, replicates via proviral intermediary DNA copies of its RNA genome in circulating monocytes, in which replication is highly restricted, and in tissue macrophages, where viral genome expression is more evident. The presence of macrophages expressing viral antigens on their surface in lungs, udder, joints or central nervous system tissues provides a focus for a local mononuclear cell inflammatory response. Factors which may contribute to macrophage activation and the development of the inflammatory response are discussed in the context of virus replication, transmission of infection and disease susceptibility.

Breed susceptibility to ovine progressive pneumonia (maedi/visna) virus.

In this retrospective study of breed differences in susceptibility to disease caused by ovine progressive pneumonia (OPP) virus, 29 Border Leicester sheep were compared with 46 Columbia sheep. As judged by frequency and severity of clinical signs and lesions attributable to the infection, Border Leicester sheep were markedly more susceptible than Columbia sheep and experimentally infected sheep were slightly more susceptible than naturally infected sheep. Differences in susceptibility to infection by the virus were not determined.

Lentiviral diseases of sheep and goats: chronic pneumonia leukoencephalomyelitis and arthritis.

This review describes the pathogenesis of a slowly progressive disease complex caused by naturally occurring nononcogenic retroviruses in sheep and goats. In nature, infections are usually clinically silent, but disease may manifest itself after prolonged incubation periods. Clinically, this is seen as dyspnea, progressive paralysis, and/or progressive arthritis. In all organs the basic lesion is inflammatory with infiltration and proliferation of lymphocytes, plasma cells, and macrophages. Other organ-specific pathologic changes such as primary demyelination in the central nervous system and degeneration of cartilaginous structures in joints accompany inflammation. The viruses infect tissue-specific macrophage populations in vivo. Viral replication in these cells is restricted to minimal levels but continues indefinitely in the animal as a result of either failure to induce specific neutralizing antibodies or antigenic drift when neutralizing antibodies develop. Consistent low-grade viral replication sets the pace for disease by providing continuous antigenic stimulation for the inflammatory cellular immune response or antibodies that localize in the target tissues. These cells and immune complexes may have adverse effects on indigenous cell populations.

Ovine progressive pneumonia: experimental intrathoracic, intracerebral, and intra-articular infections.

Three groups of 4 lambs each were experimentally infected with an isolate of progressive pneumonia virus (PPV) by intracerebral, intra-articular, or intrathoracic routes of inoculation. An additional control group was sham-inoculated by all 3 routes with identically prepared, noninfected inoculum. Sheep were killed 12 to 42 days after inoculation. A mild generalized leptomeningitis was found in 2 of the 4 lambs inoculated intracerebrally. A severe, proliferative synovitis with massive infiltration of lymphocytes and plasma cells was found in the 4 lambs inoculated intraarticularly. Germinal center formation was found in the synovial membrane 42 days after inoculation. Appreciable differences in lung morphologic features were not observed among the 4 groups. The PPV was isolated from virus-inoculated sheep from the choroid plexus, synovium, and lungs from inoculated and noninoculated sites. Nine of the 12 virus-inoculated lambs developed serum antibody to PPV, and specific antibodies were found in the synovial fluid of virus-inoculated joints. Virus was not isolated, lesions were not found, and serum antibody was not demonstrated in sham-inoculated sheep.