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.     

Isolation and characterization of a virus associated with progressive pneumonia (maedi) of sheep.

A virus with growth and morphologic characteristics of progressive pneumonia (maedi-visna) virus was isolated from the lungs of sheep with typical clinical and postmortem changes of chronic progressive pneumonia. The virus grew slowly in cultures of embryonic ovine lung cells, causing syncytial formation and degeneration. Syncytia developed much slower and involved fewer cells than reported for other similar viruses isolated from sheep. As seen with the electron microscope, the virus reproduced by budding from cell surfaces. Two types of virions were seen-a large particle (120 to 140 nm) with an electron-lucent center and dense laminated outer rim, and a small particle (80 to 110 nm) with an electron-dense core surrounded by a single membrane. Viral structures and fragments similar to the large extracellular particles were seen in the cytoplasm of a few cells. These characteristics are reported for other viruses isolated from sheep with progressive pneumonia.     

The demonstration of maedi/visna virus in sheep in Great Britain.

A virus indistinguishable from that causing maedi/visna has been isolated from a sheep flock in Great Britain. The virus was identified in cell cultures using immunofluorescent and electron microscopical techniques. The complement fixation test and the agar gel immunodiffusion test were used to assess the proportion of serological reactors within the flock. There has been no evidence of clinical disease in the flock into which foreign imports were introduced in the years prior to 1976.     

Studies in epidemiology of maedi/visna in sheep.

Lambs born to ewes from flocks with a high incidence of maedi/visna were separated from their dams at birth (group 1), or after 10 h (group 2), six weeks (group 3) or one year (group 4) and were observed for periods of up to eight years. Group 1 lambs remained free of infection while 28 per cent, 76 per cent and 81 per cent respectively of lambs in the other groups developed clinical, serological or histopathological evidence of infection during the observation period. It is therefore concluded that vertical transmission, if it occurs at all, is of little significance in the epidemiology of the disease. The number of serologically, virologically and histopathologically maedi/visna positive sheep, the time of onset of disease and the severity of lesions were related to the duration of exposure to the parent flock. In a separate trial no evidence was obtained for the transmission of maedi/visna by Muellerius capillaris larvae.     

A chronic indurative mastitis in sheep, associated with maedi/visna virus infection

A possible association of a chronic indurative mastitis with mvv (maedi visna virus) infection in sheep was investigated. Sheep of four flocks (group A), in which insufficient lamb growth apparently associated with insufficient milk production and probably related to udder induration, was a serious problem, were clinically examined in mid-lactation. The results were compared with four mvv-free flocks (group B) without such complaints. The incidence of udder induration in group A (n = 263) was about eight times higher than in group B (n = 206): 63.1 versus 8.0%. The clinical picture differed essentially between the groups. In group A the udder abnormalities were of a diffuse and indurative nature, involving both udder halves, while in group B the udder lesions were mainly nodular and often limited to one udder half. Bacteriological examination revealed a difference in infection rate of the udders (6.8% in group A versus 14.1% in group B). A substantial difference was observed in a comparison of the bacteriological infection rate of the clinically abnormal udders (5.4% in group A, versus 47.0% in group B). Serological examination with an indirect ELISA revealed 81% seropositive sheep in group A, versus 0% in group B. Twelve sheep of group A and five of group B, called for reason of mastitis, were selected for pathological examination. The gross and microscopic lesions showed a pronounced difference between both groups. In group A a diffuse interstitial mastitis with slight to moderate fibrosis and a pronounced lymphoid hyperplasia was observed. In group B the mastitis had a nodular character, with a chronic galactophoritis, extensive fibrosis, and in some cases chronic abscesses.(ABSTRACT TRUNCATED AT 250 WORDS)     

A chronic indurative mastitis in sheep,associated with maedi/visna virus infection

Summary

A possible association of a chronic indurative mastitis with mvv (maedi visna virus) infection in sheep was investigated. Sheep of four flocks (group A), in which insufficient lamb growth apparently associated with insufficient milk production and probably related to udder induration, was a serious problem, were clinically examined in mid‐lactation. The results were compared with four mvv‐free flocks (group B) without such complaints.

The incidence of udder induration in group A (n = 263) was about eight times higher than in group B(n = 206): 63.1 versus 8.0%. The clinical picture differed essentially between the groups. In group A the udder abnormalities were of a diffuse and indurative nature, involving both udder halves, while in group B the udder lesions were mainly nodular and often limited to one udder half.

Bacteriological examination revealed a difference in infection rate of the udders (6.8% in group A versus 14.1% in group B). A substantial difference was observed in a comparison of the bacteriological infection rate of the clinically abnormal udders (5.4% in group A, versus 47.0% in group B). Serological examination with an indirect ELISA revealed 81%, seropositive sheep in group A, versus 0% in group B. Twelve sheep of group A and five of group B, culled for reason of mastitis, were selected for pathological examination. The gross and microscopic lesions showed a pronounced difference between both groups. In group A a diffuse interstitial mastitis with slight to moderate fibrosis and a pronounced lymphoid hyperplasia was observed. In group B the mastitis had a nodular character, with a chronic galactophoritis, extensive fibrosis, and in some cases chronic abscesses. The lesions were often limited to one udder half Among the necropsied ewes of group A, nine showed lesions characteristic of maedi, whereas in group B no such lesions were observed.

The possible causal relation of this chronic indurative mastitis with mvv infection is discussed.     

Precipitating antibodies in experimental visna and natural progressive pneumonia of sheep

Serological responses of Icelandic sheep experimentally infected with visna virus (vv) were contrasted with responses in American Targhee sheep naturally infected with progressive pneumonia virus (PPV). Precipitating antibodies assayed by immunodiffusion were compared with the neutralising and complementing fixing antibody response. In experimental infections with vv, complement fixing and neutralising antibodies appeared early after infection and rose to high levels in all sheep, while precipitating antibodies were detected only at minimal titre. In natural infections with PPV, immune responses were less consistent and precipitating antibodies were detected more frequently than complement fixing or neutralising antibodies against PPV. These results may suggest important biological differences between the lytic fibroblast-tropic virus strains used for experimental infection of Icelandic sheep and the nonlytic macrophage-tropic strains of PPV circulating in nature. Lytic strains evoke a brisk response against the viral glycoprotein with high titre neutralising antibody while nonlytic strains induce a less consistent response to the glycoprotein.     

Effects of housing on the incidence of visna/maedi virus infection in sheep flocks

The incidence of seroconversion to visna/maedi virus (VMV) infection and its relationship with management and sheep building structure was investigated in 15 dairy sheep flocks in Spain during 3–7 years. Incidence rates were 0.09 per sheep-year at risk in semi-intensive Latxa flocks and 0.44 per sheep-year at risk in intensive Assaf flocks and was greatest for the one year old Assaf replacement flock. Separate multivariable models developed for replacement and adult flocks indicated that in both cases seroconversion was strongly associated to direct contact exposure to infected sheep and to being born to a seropositive dam. The latter effect was independent of the mode of rearing preweaning and the risk of seroconversion was similar for sheep fed colostrum and milk from a seropositive or a seronegative dam. These results are further evidence of the efficiency of horizontal VMV transmission by close contact between sheep and also suggest a inheritable component of susceptibility and resistance to infection. In contrast, indirect aerogenous contact with seropositive sheep was not associated with seroconversion as evidenced in replacement sheep housed in separate pens in the same building as adult infected sheep for one year. Consequently, VMV may not be efficiently airborne over short distances and this is important for control of infection. Moreover, there was no relationship between seroconversion and shed open areas. The latter could be related to having examined few flocks in which high infection prevalence dominated the transmission process while ventilation, may depend on a variety of unrecorded factors whose relationship to infection needs to be further investigated.     

Ovine progressive pneumonia (maedi-visna) in sheep

Ovine progressive pneumonia (OPP) is a multi-systemic disease of sheep caused by a nononcogenic exogenous retrovirus belonging to the Lentiviridae subfamily. Characteristics of the disease are chronic lymphocytic pneumonitis, encephalitis, arthritis, mastitis and vasculitis associated with progressive wasting, dyspnea, lameness, indurated udder and, rarely, paralysis. Any one or all of the characteristics may be manifest. Transmission of the virus is predominantly through the colostrum to newborn lambs, however, transmission can occur by contact and in utero. Treatment of the disease is only symptomatic and prevention of infection is only by avoiding the virus.     

Early detection of maedi-visna (ovine progressive pneumonia) virus seroconversion in field sheep samples.

The aim of this work was to investigate whether an enzyme-linked immunosorbent assay (ELISA) was useful for early detection of maedi-visna virus (MVV) infection in sheep under field conditions. An ELISA based on p25 recombinant protein and a gp46 synthetic peptide was used. Sequentially obtained serum samples (n = 1,941) were studied for 4 years. ELISA results were compared with those of the agar gel immunodiffusion (AGID) test, and results of both tests were compared with a reference result established using consensus scores for at least 2 of 3 serologic techniques (AGID, ELISA, and western blotting, which was used to resolve result discrepancies between the other 2 techniques). A total of 247 discrepancies were observed between ELISA and AGID. Of these, 131 were due to an earlier detection of 120 sera by the ELISA and 11 sera by AGID. The remaining discrepancies (116) were due to the presence of false reactions in both tests. Fewer false-negative results were found by ELISA than with AGID (6 vs. 69 sera, respectively), whereas the number of false-positive results was virtually the same for ELISA and AGID (21 vs. 20, respectively). In relation to the reference result, ELISA sensitivity and specificity were 97.8% and 98.2%, respectively, whereas values for AGID were 76.3% and 98.3%, respectively. The agreement between ELISA and the reference result was higher than that between AGID and the reference result (K value: 0.96 and 0.77, respectively). A variation in the ELISA signal (based on optical density) was observed during the study period, suggesting different antibody levels throughout the animal's life. The ELISA was useful for detecting MVV-infected sheep in field conditions and has potential for use in control and eradication programs.     

In vivo depletion of CD8+ cells does not affect primary maedi visna virus infection in sheep

T-cells have been implicated both, in promoting and reducing viral replication during lentivirus infection. CD8+ lymphocytes are believed to be important in controlling viral load through direct killing of virus-infected cells and by secretion of inhibitory chemokines and cytokines. To evaluate the role of CD8+ T-cells in the induction and control of the primary phase of a lentivirus infection, we have used a non-T-cell tropic lentivirus, maedi-visna virus (MVV), to study the initial pathogenesis and subsequent immune responses in sheep depleted in vivo of CD8+ cells. Sheep were depleted of CD8+ cells in both blood and efferent lymph for up to 14 days. No difference in MVV replication was observed in either the draining efferent lymph or lymph node of these sheep. Surprisingly, these animals displayed a normal induction of pCTL whereas the virus-specific proliferative responses were reduced. This could reflect either that a proportion of functional CD8+ lymphocytes remained in these animals, as suggested by the appearance of pCTLs, or that CD8+ cells are not required for control of primary MVV infection.     

Vasculitis associated with ovine progressive pneumonia virus infection in sheep

Vasculitis, involving small muscular arteries and arterioles, was found in 5 of 18 sheep naturally infected with ovine progressive pneumonia (OPP) virus and in 5 of 11 sheep experimentally infected with OPP virus. In order of frequency, arterial lesions were seen in carpal joint capsules, kidneys, meninges, brains, lungs, and tracheas. The lesions were intramural edema and hemorrhage, mononuclear cell infiltration, fibrinoid necrosis of media, and thrombosis. The vascular lesions were frequently associated with interstitial pneumonitis, arthritis, and encephalitis also induced by OPP virus.     

Mastitis associated with ovine progressive pneumonia virus infection in sheep

Eighteen ewes were experimentally infected with ovine progressive pneumonia virus and their mammary glands were examined for lesions and virus at 2.5 to 10 years postinoculation. Lesions were seen in 14 of 18 sheep; virus was isolated from 4 of 8 sheep. Lesion consisted of an interstitial accumulation of lymphocytes with periductal lymphoid nodules, and epithelial vacuolation and necrosis at the site of the lymphoid nodules.     

Experimental maedi infection in sheep. 1. Detection of virus, clinical course, histopathology

Eight sheep were inoculated with Icelandic maedi strain M 88; 2 sheep served as control sheep and were in close contact with the inoculated ones. Four of the sheep were inoculated via the respiratory tract with 7×10⁶ TGID50 of strain M88 and the other 4 intracerebrally with 5×10⁵ TGID50 of the same strain.Maedi M88 strain was isolated from peripheral blood leukocytes of all inoculated sheep. There was a striking difference between the 2 groups in the appearance of demonstrable viremia after inoculation. Viremia could be demonstrated in the intrapulmonarily inoculated sheep within 2–6 months but not until 8–11 months after inoculation in the intracerebrally inoculated ones. This finding is thought most probably to reflect a weak neurotropism of the strain used. After the first demonstration of viremia, maedi virus has been recovered quite reqularly in peripheral leukocytes of all intrapulmonarily inoculated sheep, but less regularly in the intracerebrally inoculated ones. Maedi virus was isolated from 1 of the uninoculated control sheep 15 months after inoculation.The first clinical case with a clinical appearance suggesting combined involvement of maedi and visna was found among the intrapulmonarily inoculated sheep, 8% months after inoculation. Histopathological examination and virus isolation confirmed maedi. The cause of paraplegia could not be confirmed. No histopathological changes were found and no virus isolation was made from the central nervous system of this animal.One of the intracerebrally inoculated sheep died suddenly without any observed clinical signs 11 months after inoculation. Histopathological examination revealed pulmonary lesions of maedi, but no visna lesions in the central nervous system, although maedi virus was isolated from various parts of brain.None of the other experimental sheep displayed clinical signs of maedi or visna during the observation period of 18 months.     

Experimental infection of sheep by caprine arthritis-encephalitis virus and goats by progressive pneumonia virus

The lentiviruses, caprine arthritis-encephalitis virus (CAEV) and progressive pneumonia virus (PPV) of sheep, cause major diseases in their respective hosts; however, the infectivity of these viruses for closely related species has not been determined. Experiments were conducted to determine whether CAEV would infect sheep and whether PPV would infect goats. Upon inoculation with CAEV, lambs developed a nonsuppurative arthritis and antibody to CAEV, and the virus was isolated up to 4 months later. Exposure of 3 lambs to CAEV-infected adult goats did not lead to demonstrable infection after 18 months. Young goats inoculated with PPV replicated the virus and developed arthritis and antiviral antibody. These results demonstrate that these distinctly different lentiviruses may infect and cause diseases in species other than their accustomed host. Presently used techniques may not be effective in differentiating which lentivirus is responsible for infection of sheep and goats. Our results also indicate that mixing sheep and goats may adversely influence attempts to eradicate lentiviruses from these species.