Duration of protection of calves against rhinovirus challenge exposure by infectious bovine rhinotracheitis virus-induced interferon in nasal secretions

Six calves inoculated intranasally with a vaccinal strain of infectious bovine rhinotracheitis (IBR) virus and 6 control calves were given a placebo. All calves were subsequently challenge exposed (by aerosol) with rhinovirus--3 of the calves from each group at 2 days after they were inoculated with IBR virus or with placebo and the remaining calves at 6 days. Nasal excretion of viruses, interferon (IFN) concentrations in nasal secretions (NS), and neutralizing antibody in sera and NS were determined. All calves given the vaccinal IBR virus subsequently had IFN in their NS. Interferon was detected as early as 1 day, reached maximal titers at 2 to 4 days, and persisted in individual calves for 5 to 10 days after inoculation. Rhinovirus shedding was not detected from IBR virus-inoculated calves whose NS contained both rhinovirus antibody and IFN at the time of challenge exposure; such calves were protected at either 2 or 6 days after IBR virus inoculation. The outcome of rhinovirus challenge exposure of calves whose NS contained IFN, but not rhinovirus antibody, varied with the day of challenge exposure. Rhinovirus excretion was detected from 2 of these calves challenge exposed 2 days after IBR virus inoculation, but was not detected from a calf challenge exposed 6 days after inoculation. However, while IFN was present in NS from the former 2 calves, rhinovirus shedding was markedly reduced as compared with that from control calves without IFN or NS antibody at the time of challenge exposure. Consistent relationship was not observed between the rhinovirus neutralizing antibody titer of calves' sera and NS. The antibody titer of NS more closely correlated with protective immunity to rhinovirus infection than did the serum antibody titer.     

Beaded agarose affinity chromatography of bovine fibroblast interferon

Bovine fibroblast interferon (BoF-IFN), produced in bovine embryonic kidney cell cultures by priming and infection with bluetongue virus, was partially purified by controlled pore glass chromatography. The partially purified BoF-IFN then was subjected to beaded agarose affinity chromatography in 2 distinct fractions--1 after the addition of 1M NaCl and the other one after the addition of 1.5M NaCl containing 50% ethylene glycol. Analysis of fractions by sodium dodecyl sulfate/polyacrylamide-gel electrophoresis revealed a broad molecular weight range (14,900 to 27,900) for IFN eluted by 1M NaCl, and 2 discrete molecular weight ranges (16,000 to 19,500 and 28,300 to 34,000) for IFN eluted by 1.5M NaCl containing 50% ethylene glycol. The specific activity of the IFN eluted with 1.5M NaCl containing ethylene glycol was 2.85 X 10(6) U/mg of protein, compared with 5.7 X 10(5) U/mg of protein in the controlled pore glass-purified IFN.     

Partial purification and characterization of bovine fibroblast interferon

Bovine fibroblast interferon (BoF-IFN), produced in primary bovine embryonic kidney cell cultures after priming and infection with bluetongue virus, was purified by controlled pore glass (CPG) chromatography to a specific activity of 10(6) U/mg of protein, with 40% recovery of the original activity. The crude IFN was concentrated more than sevenfold during purification. This proved to be a relatively simple, practical method of obtaining sufficient quantities of partially purified natural BoF-IFN for further studies. The CPG-purified BoF-IFN was further concentrated by sequential ultrafiltration and was analyzed by sodium dodecyl sulfate/polyacrylamide-gel electrophoresis (SDS-PAGE). Interferon, recovered from denaturing conditions either by dialysis against phosphate-buffered saline solution or by dilution in cell culture medium containing 10% fetal bovine serum, migrated as a single stainable protein with molecular weight of 21,000 on analytic SDS-PAGE gels. Recovered IFN activity from preparative SDS-PAGE totalled 8.7% of that applied. Attempts to further purify CPG-purified BoF-IFN by zinc chelate affinity chromatography were unsuccessful.     

Effect of colostral antibody on bovine leukemia virus infection of neonatal calves

Pairs of newborn calves were exposed to bovine leukemia virus (BLV) when they were given their 1st colostrum feeding. Calves that were given 10(6) BLV-infected lymphocytes in colostrum free of BLV-specific antibody became infected. Calves that were fed 10(7), 10(8), or 10(9) infected lymphocytes in colostrum that contained BLV-specific antibody did not become infected. One of 2 calves inoculated intradermally with 250,000 infected lymphocytes was protected by colostral antibody, but the other was not. Colostral antibody titers in the unprotected calf decreased normally until the calf was 4 months old and then increased markedly; this pattern indicates that the presence of colostral antibody may have prolonged the latent period of the BLV infection.     

Trypanosoma evansi infection in bovine and buffalo calves in Indonesia.

Fifteen bovine and 11 buffalo calves born on different farms in a Trypanosoma evansi-endemic area of West Java were monitored for the presence of T. evansi and T. evansi antibody at monthly intervals until they were 12 months of age. Fifty percent of the bovine and 83% of the buffalo calves sampled in the first month of life were antibody positive. This antibody was considered to be of colostral origin. Antibody developing later in life persisted for up to 12 months and was considered to have arisen in response to T. evansi infection. No protective function could be ascribed to the colostral antibody.     

Effect of recombinant DNA-derived bovine alpha-1 interferon on transmissible gastroenteritis virus infection in swine

Recombinant DNA-derived bovine interferon alpha 1-1 (BoIFN) inhibited replication of both vesicular stomatitis virus and transmissible gastroenteritis virus in cultures of swine testicular cells. Newborn pigs were orally inoculated with BoIFN and subsequently had interferon in their gastric contents and serum; however, interferon was found only occasionally in intestinal washings. Incubation of BoIFN with gastric contents from a newborn suckling pig did not affect antiviral activity, whereas intestinal (small intestine) contents from the same animal inactivated BoIFN within 1 minute. Beginning at 6 hours of age, newborn, colostrum-deprived pigs were given 1 mg of BoIFN orally every 12 hours. These pigs were not protected against challenge exposure to virulent transmissible gastroenteritis virus at 48 hours of age; disease and mortality were similar for these pigs and for control pigs not given BoIFN prior to challenge exposure. The BoIFN did not impair growth rate of pigs and did not cause obvious disease or lesions.     

Effect of experimentally induced type II bovine viral diarrhea virus infection on platelet function in calves

OBJECTIVE: To evaluate platelet aggregation responses in calves experimentally infected with a thrombocytopenia-inducing type II bovine viral diarrhea virus (BVDV) isolate (BVDV 890). ANIMALS: 9 neonatal male Holstein calves. PROCEDURE: 5 calves were inoculated with BVDV 890, and 4 were used as controls. Platelet aggregation studies and attempts to isolate BVDV from platelets were performed 2 days before, the day of, and every 2 days for 12 days after inoculation. Platelet function was assessed by means of optical aggregometry, using adenosine diphosphate and platelet-activating factor as agonists. Bovine viral diarrhea virus was isolated from purified platelet preparations by use of an immunoperoxidase monolayer assay. RESULTS: Maximum percentage aggregation and slope of the aggregation curve decreased over time in calves infected with BVDV. Bovine viral diarrhea virus was not isolated from platelets from control calves, but it was isolated from infected calves from 4 through 12 days after inoculation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that platelet function may be depressed in calves infected with type II BVDV. Although the mechanism for altered platelet function was not determined, it likely involved an increase in the percentage of aged platelets in the circulation, a direct virus-platelet interaction, or an indirect virus-platelet interaction. Platelet dysfunction, in addition to thrombocytopenia, may contribute to the hemorrhagic syndrome associated with acute type II BVDV infection in calves.     

Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves

OBJECTIVE: To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves. ANIMALS: Eleven 6- to 8-week-old Holstein bull calves. PROCEDURES: Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined. RESULTS: Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed. CONCLUSIONS AND CLINICAL RELEVANCE: BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease. IMPACT FOR HUMAN MEDICINE: Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.     

Protection of colostral antibodies against bovine leukemia virus infection in calves on a California dairy.

A three-year prospective study involving 244 calves was undertaken on a California dairy to evaluate the protective role of colostral antibodies against bovine leukemia virus (BLV) infection in calves. Calves were followed from birth to the time they left their individual hutch (TLIH), at about 90 days of age. The probability of being infected at TLIH and the daily risk of infection between birth and TLIH were modelled using the logistic and the Cox models, respectively. Calves with no detectable antibodies during the first week of life were up to 2.00 and 2.75 times more likely to be infected at TLIH compared to calves with low and high concentrations of antibodies during the first week of life, respectively (p = 0.01). When the daily risk was modelled, calves without antibodies at the estimated day of infection were up to 3.4 and 11.6 times more likely to become infected than calves with low and high concentrations of antibodies on that day, respectively (p less than 0.001). Results indicated that calfhood infection may be reduced by about 45% through the feeding of colostrum with BLV antibodies. Further reduction in infection may be possible by feeding calves milk powder, milk replacer, and/or milk from noninfected cows. Results also indicated that quantification of the effect of a time-dependent risk factor, such as colostral antibody concentration, might be affected if treated as a fixed factor.     

Effect of human leukocyte A interferon on prevention of infectious bovine rhinotracheitis virus infection of cattle

Human leukocyte A interferon was evaluated for its ability to prevent infectious bovine rhinotracheitis virus-induced respiratory tract disease in cattle. Weanling calves were treated daily for 1 week with 50 X 10(6) U of interferon, intranasally (by nebulization) and IM, and inoculated with infectious bovine rhinotracheitis virus on the first day of treatment. Respiratory tract disease was less severe in treated as compared with nontreated calves which were given only infectious bovine rhinotracheitis virus, and infection in the treated calves occurred later than in the untreated calves. Viral shedding and appearance of viral neutralizing antibodies occurred later in treated calves than in calves given only virus. Because several calves in a treatment group were housed together, whether the late appearance of infection in some interferon-treated calves was due to emergence of suppressed virus or to horizontal transmission from calves shedding virus could not be determined. One calf in the interferon-treated group developed antibody to human interferon and a few treated calves had transient elevation of hepatic enzymes. Interferon-treated calves developed a high temperature which subsided on termination of treatment. Production of disease was considerably dependent on the amount of virus and interferon given, since calves given 300 times more virus and approximately half as much interferon showed no evidence of protection against infection.