The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP2 in liver and muscle of rats

OBJECTIVE: To determine efficacy of a vaccine containing modified-live bovine viral diarrhea virus (BVDV) type 1 for protecting pregnant cows and their fetuses against virulent heterologous BVDV type 1. DESIGN: Randomized controlled cohort study. ANIMALS: 18 yearling beef heifers seronegative for BVDV and negative when tested for BVDV by virus isolation. PROCEDURE: Cattle were randomly assigned to control (unvaccinated; n = 6) or vaccinated (12) groups. Vaccinated heifers were given a combination vaccine containing modified-live BVDV type 1 comprising a cytopathic (NADL) strain. All 18 heifers were then bred and challenge-exposed between 70 and 75 days of gestation with BVDV type 1, administered intranasally. Cattle were monitored, and infection status of offspring was determined after parturition. Antibody concentrations of vaccinated and control heifers were also monitored. RESULTS: All 6 calves from control heifers had positive results on multiple virus isolation tests and were considered persistently infected. In comparison, only 2 calves from vaccinated cows had positive results on virus isolation tests and were considered persistently infected. One vaccinated heifer aborted, but the fetus was not persistently infected, and the abortion was not attributed to BVDV infection. CLINICAL IMPLICATIONS: Analysis of these data indicated that a single dose of a modified-live NADL-derived BVDV type 1 vaccine will confer protection to dams and their fetuses against challenge-exposure to heterologous BVDV type 1 organisms.     

The occurrence of BVD virus infections in lower Austrian dairy farms

Bulk tank milk samples from 5,024 dairy herds in Lower Austria were tested by ELISA for antibodies to bovine virus diarrhoea virus (BVDV). Approximately 54 per cent of the herds had a low level of bulk tank antibody unsuspected of recent infection with BVDV. In 512 herds, which had a high level of bulk tank antibody suggestive of recent infection with BVDV, milk samples from 5-10 primiparous cows, respectively were tested by ELISA for antibodies to BVDV. In 287 (56.1%) of these 512 herds only antibody-negative primiparous cows were detected. In 759 herds blood samples from 8-10 young stock, respectively were tested by ELISA for antibodies to BVDV. The majority of the tested animals was seronegative in 583 (76.8%) herds. The whole stock from 154 herds was tested for persistent BVDV infections. From 51 herds in all 149 cattle persistently infected with BVDV were detected. Because of the low prevalence of BVDV infections it seems possible to control BVDV without vaccination in Lower Austrian dairy farms.     

Congenital abnormalities in newborn calves after inoculation of pregnant cows with Akabane virus

A fresh isolate of Akabane virus was inoculated intravenously into 11 seronegative pregnant cows at 62 to 96 days of gestation. Two of the cows were slaughtered 18 days post-inoculation, and the fetuses were examined; the remaining cows were allowed to give birth. All the inoculated cows developed viremia and neutralizing antibody for the virus, indicating that the cows were actually infected with the virus, although fever or any other clinical abnormalities were not noted. The virus further infected the fetuses. This was proved by virus isolation in one of the two fetuses from the slaughtered cows, and polymyositis was noted in both fetuses. Six of seven calves born alive had anti-Akabane antibody in their precolostral sera, indicating that in utero infection with the virus took place in these calves. Some of the in utero-infected calves demonstrated congenital abnormalities such as cerebral defect, hydranencephaly, and arthrogryposis. These findings provide additional evidence that Akabane virus is the etiological agent of epizootic abortion and congenital arthrogryposis-hydranencephaly syndrome in cattle.     

Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus

OBJECTIVE: To determine efficacy of a modified-live type-I isolate of bovine viral diarrhea virus (BVDV) vaccine in protecting calves from infection with a virulent type-II isolate, and to determine which type of immune response (i.e., humoral or cellular) correlates with protection. DESIGN: Prospective study. ANIMALS: 28 neonatal Holstein and Holstein-cross calves. PROCEDURE: Within 18 hours of birth, calves received maternal colostrum or were fed pooled colostrum. On days 7 to 10 after birth, calves were determined to be seropositive (n = 16) or seronegative (12) for antibodies to BVDV on the basis of ELISA and virus neutralization test results. Seropositive and seronegative 10- to 14-day-old calves were then given a combined vaccine that contained a modified-live type-I isolate of BVDV or a similar vaccine that lacked protection against bovine viral diarrhea. All calves were inoculated intranasally approximately 21 days after vaccination with a virulent type-II isolate of BVDV. Clinical and immunologic variables, including clinical scores, rectal temperatures, results of CBC with lymphocyte subset analysis, antibody responses, and cell-mediated immune responses, were monitored for 14 days after inoculation. RESULTS: Seronegative-unvaccinated calves developed severe disease and required euthanasia. Vaccination of seronegative calves with a modified-live type-I isolate had a disease-sparing effect as did passive transfer of colostral antibodies to BVDV. Clinical scores were not significantly different between seropositive-vaccinated and seropositive-unvaccinated calves after viral inoculation. CLINICAL IMPLICATIONS: A single dose of a modified-live type-I isolate of BVDV vaccine protects young calves from clinical signs of disease associated with type-II isolates.     

Delirium and persistent dyskinesia induced by a lithium-neuroleptic interaction

Vaccination with live cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) is often used for control of this disease. In animals which are persistently infected with noncytopathogenic (ncp) BVDV this can lead to the outbreak of mucosal disease (MD). To simulate vaccination of such animals and to monitor the clinical-virological course after superinfection, nine clinically healthy calves which were persistently viremic were superinfected with different cp BVDV strains. One animal succumbed to early onset MD within three weeks after superinfection. During the observation period of 18 months four animals developed severe clinical signs. While two animals developed late onset MD, the other two had to be euthanized due to clinical signs which could not be related to the superinfecting BVDV. These results indicated that after superinfection or vaccination of persistently infected calves with cp BVDV the probability of developing early and/or late onset MD is significantly increased. The risks arising from uncritical vaccination of herds with unknown virological status in relation with the control of BVDV conforming to the actual official guidelines are discussed.     

An experimental study of a concurrent primary infection with bovine respiratory syncytial virus (BRSV) and bovine viral diarrhoea virus (BVDV) in calves

Experimental infections with bovine respiratory syncytial virus (BRSV) and bovine viral diarrhoea virus (BVDV) were performed to study the effect of concurrent BRSV and BVDV infections. Twelve seronegative calves, in 3 groups, were inoculated on a single occasion with pure BRSV (group A), BRSV and noncytopathogenic BVDV (group B) or mock infected (group C). Mild respiratory symptoms were recorded 4 to 5 days post inoculation (dpi) in group A and group B calves. One calf in group A was severely affected and required medical treatment. In group B, fever (40.7-41.4 degrees C) was prominent 7 to 8 dpi. Only calves in group B were BVDV positive in purified lymphocytes at 2 to 14 dpi and showed increased serum interferon levels, with a peak at 4 dpi, indicating BVDV to be responsible for inducing the rise. BRSV was detected in lung lavage fluids up to 7 dpi for group A calves, compared to 11 dpi for group B and calves in this group also seroconverted later displaying lower BRSV titers. The time lag before an antibody response and the titers recorded in group B, indicated that the duration of BVDV infection in lymphocytes negatively influenced the capacity to mount a BRSV antibody response.     

Experimental infection with Babesia divergens in cattle persistently infected with bovine virus diarrhoea virus

Nine Norwegian Red cattle, aged 7-14 months, persistently infected with bovine virus diarrhoea virus (BVDV) were inoculated with a Swedish strain of Babesia divergens. Six persistently infected cattle of the same age and breed were kept as controls. Blood and serum samples were collected regularly during the observation period. Rectal temperatures were recorded every morning for 25 days post infection, and the animals were examined clinically on a daily basis. Sera were examined for antibodies to B. divergens by indirect immunofluorescence antibody test (IFAT). Eight of the infected animals developed fever of 2-5 days duration. Babesia divergens organisms appeared in the erythrocytes of all infected animals on the day after inoculation. The parasitaemia lasted for 4-11 days. One animal had a transient haemoglobinuria. Compared with the control group, there was a 20% decrease in the haematocrit. There was a transient lymphopenia and thrombocytopenia during the period of fever. There were no differences in mean numbers of neutrophils between the two persistently infected groups. Compared with cattle free of BVDV, the persistently infected cattle had consistently lower total leucocyte count that was mainly due to decreased mean numbers of neutrophils and monocytes. All infected animals develop antibodies > or = 1:1280 between day 7 and 10 post infection. The magnitude of the antibody response was considerably lower than that of BVDV-free animals inoculated with the same strain and dosage of B.divergens.     

Organ and tissue distribution of the antigen of the cytopathogenic bovine virus diarrhea virus in the early and advanced phase of experimental mucosal disease

To study the development of lesions in mucosal disease, the spread of cytopathogenic (cp) bovine virus diarrhea virus (BVDV) to different organs was examined in relation to the time post inoculation (pi). Mucosal disease was induced in 15 persistently viremic cattle from two herds by intranasal inoculation with antigenically similar cp BVDV strain. This strain reacted with one additional monoclonal antibody when compared to the corresponding herd-specific non cytopathogenic (ncp) isolate. Twelve cattle were euthanized at days 3, 5, 7, 9 and 13 pi in the early phase before they developed clinical signs of mucosal disease, three in the advanced phase when they were moribund and three served as controls. Antigen of the cp BVDV strains was selectively detected in tissue sections by immunohistochemistry. In the early phase, varying amounts cp BVDV were present most consistently in tonsils, lymph nodes, Peyer's patches and lymphoid nodules in the large intestine. In the lymphoid tissues, first a few cells in single lymphoid follicles, then groups of lymphoid follicles contained antigen. In intestinal epithelium, cp BVDV antigen was found focally in the early phase of mucosal disease. Its diffuse distribution in the late phase corresponded with clinical signs of diarrhea.     

Epidemiology of bovine virus diarrhoea in cattle on communal alpine pastures in Switzerland

The goal of this study was to determine the influence of communal pasturing on the spread of bovine virus diarrhoea (BVD). The investigation involved 990 Swiss Braunvieh cattle from 149 different owners on seven communal pastures in the Swiss Alps. Prior to pasturing, blood samples were collected from all animals for examination for BVD antigen and antibodies. Serological examinations were also performed during and after pasturing to determine possible increases in seroprevalence and to determine whether seroprevalence was different on pastures with and without persistently infected cattle. At the start of pasturing, nine (0.9%) animals were persistently viraemic. On three alpine pastures, no persistently viraemic animals were detected. The prevalence of persistently infected cattle on the remaining four pastures varied from 0.3 to 3.9%. Of the 990 animals tested at the start of pasturing, 632 (63.3%) were seropositive. Seroprevalence differed among pastures and varied from 21.8 to 85.9%. During the summer, seroprevalence increased on all pastures surveyed, and at the end of the pasture season, 778 (80.1%) of the 971 cattle that were examined twice were seropositive. The incidence of seroconversion was significantly higher on pastures with persistently infected cattle compared with those without; it ranged from 32.7 to 100.0% in the former and from 6.0 to 22.2 in the latter. The results of this study suggest that communal alpine pasturing does play a role in the spread of BVD. The extent of this role depends on the presence of persistently infected animals.     

Glucocorticoid binding in mammary tissue slices of cattle in various reproductive states

Unlabeled cortisol and dexamethasone reduced tritiated cortisol and tritiated dexamethasone binding to 700 X g supernatant and precipitate fractions of mammary tissue slices from virgin heifers and from multiparous cows that were 1-mo prepartum (nonlactating), lactating (non-pregnant), or dry (nonpregnant, nonlactating). Unlabeled progesterone, testosterone, and 17beta-estradiol had no effect on tritiated glucocorticoid binding in 700 X g supernatant and precipitate fractions from these mammary tissue slices. The 700 X g fractions in mammary tissue slices from all cattle bound cortisol and dexamethasone with high affinity (Kd 10-10M). There were 1263 and 1955 molecules of cortisol and dexamethasone bound per mammary cell, respectively, in mammary tissue slices from lactating non-pregnant cows; in comparison virgin heifers bound 413 and 651 molecules of cortisol and dexamethasone; dry, non-pregnant cows bound 336 and 536 molecules of cortisol and dexamethasone; and 1-mo prepartum nonlactating cows bound 532 molecules of cortisol. Mammary tissue slices from cattle in reproductive states examined contained a major non-specific component which bound cortisol in both 700 X g tissue fractions. Since mammary tissue slices from lactating cattle bound more molecules of glucocorticoids than mammary slices from cattle in other reproductive states, we speculate specific glucorticoid binding may be associated with lactation.     

Effects of vaccination with a Moraxella bovis bacterin on the subsequent development of signs of corneal disease and infection with M bovis in calves under natural environmental conditions

A vaccination study was conducted for infectious bovine keratoconjunctivitis (IBK) in 440 purebred Hereford cattle (cows and their newborn calves) of the USDA Meat Animal Research Center cattle herd at Clay Center, Ne. The cattle were allotted to 4 groups: 60 calves were vaccinated with an autogenous Moraxella bovis bacterin (group 1); 60 calves that were matched with group 1 calves were designated nonvaccinated matched controls (group 2); 99 calves were peer group nonvaccinated controls (group 3); and 219 cows, the dams of the calves, were nonvaccinated consorts (group 4). The infection rates in cattle groups 1, 2, 3, and 4 during the summer were 96.6, 98.3, 100, and 79.1%, respectively, and the disease rates were 90, 93, 85, and 20%. The infection and the disease rates were significantly (P less than 0.01) different between claves and cows. The disease rate was also significantly different between older and younger cows. A larger percentage of the affected calves and cows had mild or moderate (61%) signs of IBK rather than severe (39%) signs. The rate of body weight gain was reduced in calves with severe signs of IBK. The results seemed to indicate that little would be gained by vaccinating cattle against IBK under the conditions of study.     

Reproductive performance of cows mated to and preweaning performance of calves sired by Brahman vs alternative subtropically adapted breeds

Comparisons involving Brahman and Brahman-derivative (Brangus, Santa Gertrudis, Beef-master, Simbrah, Braford) sires indicate the following: 1) cows mated to Brangus and Santa Gertrudis bulls had a shorter gestation length than cows mated to Brahman bulls, 2) calves sired by Brangus and Beefmaster bulls were lighter at birth and weaning than calves sired by Brahman bulls, and 3) birth and weaning weights were similar for calves sired by Santa Gertrudis and Brahman bulls and for calves sired by Simbrah and Brahman bulls. Comparisons involving Brahman and other Zebu (Sahiwal, Nellore, Gir, Indu-Brazil, Boran, Romana Red) sires indicate that gestation length was slightly longer for cows mated to Sahiwal and Nellore bulls and that, relative to the Brahman, birth and weaning weights were similar to or lighter for calves sired by bulls of the other Zebu breeds. The only exception to this pattern was birth weight of Indu-Brazil-sired calves, which were heavier than calves sired by Brahman bulls. Comparisons involving Brahman and non-Zebu subtropically adapted (Tuli, Senepol) sires indicate that cows mated to Tuli bulls had a slightly shorter gestation length than cows mated to Brahman bulls and that birth and weaning weights of calves sired by Tuli and Senepol bulls were lighter than those of calves sired by Brahman bulls.     

Prevalence of antibodies to bovine virus diarrhoea virus and other viruses in bulk tank milk in England and Wales

Bulk tank milk samples from 1070 dairy herds in England and Wales were tested by ELISA for antibodies to bovine virus diarrhoea virus (BVDV). A subset of 341 herds was tested by ELISA for antibodies to bovine herpesvirus 1 (BHV-1), bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV). None of the herds had less than 40 dairy cows and none had been vaccinated against BVDV. The prevalence of BVDV antibody-positive herds in the national population was estimated at 95 per cent and approximately 65 per cent of the herds had a high level of bulk tank antibody suggestive of recent infection with BVDV. Dairy herds in East Anglia and the south-east of England had a significantly lower risk of being BVDV antibody-positive than herds in the rest of England and Wales. However, these regional differences tended to diminish with increasing herd size. Around 69 per cent of the herds were BHV-1 antibody-positive and all the herds were antibody positive to BRSV and BCV. Comparison with earlier serological surveys revealed that there had been little change in the prevalence and distribution of BVDV antibody-positive herds in England and Wales over the last 20 years, but that there had been an increase in the prevalence of BHV-1 antibody-positive herds.     

Teratogenicity and toxicity of coniine in cows, ewes, and mares

Cows, ewes, and mares varied considerably in susceptibility to toxicoses from the oral administration of the piperidine alkaloid, coniine. Cows were most susceptible and ewes least. Only calves had teratogenic effects from maternal administration of coniine during gestation; lambs and foals were apparently resistant. Results suggest that the marked differences between cattle and sheep are probably not due to variation in gut absorption or rumen metabolism.     

Cytopathogenicity of a pestivirus correlates with a 27-nucleotide insertion

Cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strains are generated in cattle persistently infected with noncytopathogenic (noncp) BVDV.cp BVDV strains are considered crucial for the development of fatal mucosal disease. Comparative analysis of cp and noncp BVDV strains isolated from one animal suffering from mucosal disease revealed that the genomes of the cp BVDV strain (CP7) and the corresponding noncp BVDV strain (NCP7) are highly homologous. However, only the genome of CP7 contains an insertion of 27 nucleotides in the NS2 coding region. The inserted sequence represents a duplication of bases 4064 to 4090 of the viral genome, located between the formerly neighboring nucleotides 4353 and 4354. Parts of the viral polyproteins of CP7 and NCP7 were expressed in the T7 vaccinia virus system. These studies revealed that the insertion identified in the CP7 genome is necessary and sufficient for the induction of NS2-3 cleavage. Since the expression of NS3 is strictly correlated to cp BVDV, the insertion identified in the genome of BVDV CP7 represents most likely the relevant mutation leading to the evolvement of CP7 from NCP7.     

Detection of serum antibody responses in cattle with natural or experimental Neospora infections

Parasite-specific antibody responses were detected using an indirect fluorescent antibody (IFA) test in cattle that were naturally or experimentally infected with Neospora parasites. The test was developed using Neospora tachyzoites isolated from an aborted bovine fetus and grown in bovine cell cultures (isolate BPA1). In all cases, infections were confirmed by the identification of Neospora tachyzoites and/or bradyzoite cysts in fetal or calf tissues using an immunoperoxidase test procedure. Fifty-five naturally infected cows that aborted Neospora-infected fetuses had titers of 320-5,120 at the time of abortion. The titer of 6 cows that were serologically monitored over a prolonged period decreased to 160-640 within 150 days after they aborted infected fetuses. Two of the cows showed an increase in their Neospora titers during their subsequent pregnancy, and they gave birth to congenitally infected calves that had precolostral titers of 10,240-20,480. Postcolostral titers of these calves and of 4 other calves with congenital Neospora infections were all > or = 5,120, whereas calves with no detectable parasites had titers < or = 160. Two pregnant heifers that were experimentally infected with the BPA1 isolate at approximately 120 days gestation seroconverted to Neospora antigens within 9 days and developed peak titers of 5,120 and 20,480 within 32 days of infection. The fetus taken by caesarean section 32 days postinfection from 1 heifer and the full-term calf born to the other had Neospora titers of 640 and 10,240, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of antibodies to bovine viral diarrhoea virus (BVDV) and characterization of genomes of BVDV from Brazil

An ELISA for the detection of antibodies to bovine viral diarrhea virus (BVDV) was developed based on antigens derived from a genotype I BVDV strain isolated in Switzerland. Using monoclonal antibodies we showed that this antigen contained the conserved non-structural protein NS3 whereas it essentially lacked the more strain-specific E2 surface glycoprotein. This ELISA has a sensitivity of 97.5% and a specificity of 99.2% as compared to the serum neutralization test (SNT). Preliminary experiments showed that this ELISA reliably detects antibodies to BVDV strains circulating in Brazil. Serum samples obtained from 430 adult cattle on 19 farms of the State of Rio Grande do Sul (Brazil) and one farm from Corrientes (Argentina) were tested for antibodies by means of this ELISA. We found antibodies in 56% +/- 15.1% of the cattle sera tested, which indicates that, in Brazil, the prevalence of infection with BVDV is similar to that found in Europe and the USA. Our sequence analysis of two BVDV isolates showed that BVDV of both genotypes I and II circulate in Brazil.     

Culling associated with Neospora caninum infection in dairy cows

OBJECTIVES: To estimate the extent to which cows infected with Neospora caninum were culled, compared with noninfected cows, and to identify differences in reasons for culling between infected and noninfected cows. ANIMALS: 442 Holstein cows on a commercial dairy with 36% seroprevalence for N caninum. PROCEDURE: Culling of cows was done after first calving without knowledge of N caninum serologic status. RESULTS: Risk of a seropositive cow dying was not different from that of a seronegative cow (P = 0.50). Seropositive cows were culled 6.3 months earlier than seronegative cows, and had a 1.6 times greater risk of being culled, compared with seronegative cows (P = 0.004), after adjusting for culling risk associated with abortion. For cows culled for low milk production, culling risk for a seropositive cow was twice that for a seronegative cow (P = 0.007). CONCLUSIONS: The economic impact of N caninum infection in dairy cattle can be expected to extend beyond that for abortion alone. Costs of the disease also may include premature culling and diminished milk production. CLINICAL RELEVANCE: Plans to control N caninum infection on dairies should include consideration that benefits may include reduction in premature culling and increase in milk production.     

Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques

Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful animal model to explore novel strategies to reduce perinatal human immunodeficiency virus (HIV) infection. The availability of two easily distinguishable virus isolates, SIVmac251 and the simian/human immunodeficiency virus chimera SHIV-SF33, allows tracing the source of infection following inoculation with both viruses by different routes. In the present study, we evaluated the efficacy of pre- and postinoculation treatment regimens with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) to protect newborn macaques against simultaneous oral SIVmac251 and intravenous SHIV-SF33 inoculation. Untreated newborns became persistently infected following virus inoculation. When three pregnant macaques were given a single subcutaneous dose of PMPA 2 hr before cesarean section, their newborns became SIV-infected following SIV and SHIV inoculation shortly after birth. In contrast, when four newborn macaques were inoculated simultaneously with SIV and SHIV, and started immediately on PMPA treatment for 2 weeks, only one animal became persistently SIV-infected; the remaining three PMPA-treated newborns, however, had some evidence of an initial transient virus infection but were seronegative and healthy at 8 months of age. Our data demonstrate that PMPA treatment can reduce perinatal SIV infection and suggest that similar strategies may also be effective against HIV.