Search

BackgroundThe prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations.ObjectiveDetermine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2 O2 /I- ) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo.AnimalsSixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd.MethodsIn vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2 O2 /I- system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I- concentration.ResultsBovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2 O2 /I- reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax  = 181 (1,420 μM I), T12 , a sufficient concentration to inactivate these pathogens in vitro.Conclusions and clinical importanceIn vitro, the LPO/H2 O2 /I- system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections.

Veterinary college curricula are generally offered through face-to-face lectures and laboratories. However, because of the COVID-19 global pandemic, entire veterinary curricula throughout the United States were forced to utilize remote learning with large portions of courses provided through synchronous or asynchronous delivery platforms employing video portal systems in spring 2020. The purpose of this study was to examine the satisfaction of veterinary students who were taught through remote learning with the option of synchronous live streaming lectures or asynchronous recorded lectures for a portion of 1 semester. This study also examined student satisfaction by comparing two cohorts of students taught via remote learning during the same semester (semesters 2 and 4 in the curriculum). The sample population consisted of a convenience sample of 242 veterinary students from one large southeastern veterinary college, who were asked to complete the end-of-semester course evaluation, which included five statements pertaining to remote learning. This study was performed to provide insight into changes that could be considered in the future as veterinary education seeks to utilize advancing technology and increase flexibility in learning while still providing high-quality education. Measures of dispersion and frequency were used to analyze the data. Veterinary students in this study preferred watching recorded lectures to streaming live lectures. Additional responses indicated overall agreement from both groups regarding lecture length, support for remote learning, and available resources for remote learning.

The liver is subject to toxic insult due to its role in the metabolism of exogenous substances and the direct filtration of blood from the portal circulation, which carries absorbed toxins from the gastrointestinal system. Metabolism of xenobiotics in the liver is facilitated by high concentrations of cytochrome P450 enzymes, which catalyze biotransformation of foreign substances; conjugation of toxin metabolites increases their solubility and enhances excretion. An understanding of the common hepatotoxins and the circumstances that lead to their exposure in cattle will aid the clinician in recognizing clinical syndromes and submitting appropriate diagnostic samples for confirmation of suspected diagnoses., Competing Interests: Disclosure The author has no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Studies suggest that high cortisol resulting from lameness-associated pain decreases testosterone and disrupts spermatogenesis leading to decreased fertility. The objective of this study was to investigate the effect of lameness on cortisol and testosterone concentrations and breeding soundness examination of beef bulls presented to a veterinary teaching hospital. Bulls, two-years of age or older, that presented for lameness, foot trim, and/or breeding soundness examination were enrolled. Blood samples were collected for cortisol and testosterone evaluation. A complete breeding soundness examination (BSE) was performed in all bulls. Subsequently, a complete lameness examination was performed, and limb/foot lesions recorded. A blinded evaluator used a lameness score of 1-5 to classify each bull as lame (>1) or not-lame (1). A total of 60 bulls were enrolled (34 with a satisfactory BSE and 26 with an unsatisfactory BSE result). Cortisol and testosterone were not different between the unsatisfactory and satisfactory groups (P = 0.26 and 0.32, respectively). The most common limb/foot lesions found in the unsatisfactory and satisfactory groups were laminitis-related (61.50% and 41.20%, respectively). There was no difference in the proportion of lame and not-lame bulls in the unsatisfactory and satisfactory groups (P = 0.17). The odds of a satisfactory BSE result were 4.40 times higher in not-lame bulls when compared with lame bulls. Therefore, lameness is associated with an unsatisfactory BSE result in beef breeding bulls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bovine viral diarrhea virus (BVDV) was first reported 75 years ago and remains a source of major financial and production losses in the North American cattle industry. Currently, control methods in North America primarily center around biosecurity and vaccination programs; however, despite high levels of vaccination, the virus persists in the cattle herd due at least in part to the often-insidious nature of disease and the constant viremia and viral shedding of persistently infected animals which act as a reservoir for the virus. Continued development of targeted antivirals represents an additional tool for the prevention of BVDV-associated losses. Currently, in vivo studies of BVDV antivirals are relatively limited and have primarily been directed at the RNA-dependent RNA polymerase which represents the viral target with the highest potential for commercial development. Additional live animal studies have explored the potential of exogenous interferon treatment. Future research of commercial antivirals must focus on the establishment and validation of in vivo efficacy for compounds with demonstrated antiviral potential. The areas which provide the most viable economic justification for the research and development of antivirals drugs are the fed cattle sector, outbreak control, and wildlife or animals of high genetic value. With further development, targeted antivirals represent an additional tool for the management and control of BVDV in North American cattle herds., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The gut microbiome provides important metabolic functions for the host animal. Bacterial dysbiosis as a result of bacterial, viral, and parasitic gastrointestinal infections can adversely affect the metabolism, productivity, and overall health. The objective of this study is to characterize the commensal microbiome present in the lumen and the mucosal surface of the duodenum of cattle, as we hypothesize that due to metabolic processes and or host proprieties, there are differences in the natural microbiota present in the mucosal surface and luminal contents of the bovine duodenum. Duodenal lumen contents and mucosal biopsies were collected from six dairy crossbred yearling steers. A flexible video-endoscope was used to harvest biopsy samples via a T shaped intestinal cannula. In order to assess as much environmental and individual steer microbiota variation as possible, each animal was sampled three times over a 6 week period. The DNA was extracted from the samples and submitted for16S rRNA gene Ion Torrent PGM bacterial sequencing. A detailed descriptive analysis from phylum to genus taxonomic level was reported. Differences in the microbiome population between two different sites within the duodenum were successfully characterized. A great and significant microbiota diversity was found between the luminal and mucosal biopsy At the phylum taxonomic level, Firmicutes, and Bacteroidetes composed over 80% of the microbiome. Further analysis at lower taxonomic levels, class, family, and genus, showed distinct diversity and distribution of the microbiome. Characterizing the gastrointestinal microbiome in vivo is imperative. The novelty of this study is the use of live cattle undergoing customary husbandry allowing real-time analysis of the duodenum microbiome contributing to the literature with respect to the bovine duodenum microbiome., (Copyright © 2020 Stockler, Higgins, Hallowell, Groover, Hiltbold, Newcomer and Walz.)

Bovine viral diarrhea virus (BVDV) is one of the most economically important viruses of cattle, but this pathogen is also able to infect pigs, camelids, and a wide range of domestic and wild ruminants. BVDV isolates circulating in animal populations are genetically and antigenically highly diverse. Acute BVDV infections in cattle cause the introduction of many substitutions in the viral genome. Serial infection of pregnant sheep with a BVDV-1b isolate of bovine origin was also associated with great numbers of substitutions. To our knowledge, genomic changes arising during BVDV infections in swine have not been investigated. The purpose of this study was to investigate the changes occurring in the open reading frame (ORF) of BVDV during serial infection of pregnant swine with a BVDV isolate of bovine origin. The BVDV-1b isolate AU526 was serially passaged in six pregnant gilts, two of which gave birth to live piglets congenitally infected with BVDV. The complete ORF sequences of 14 BVDV isolates obtained from pregnant gilts and their piglets were determined. Their analysis revealed that serial transmission of AU526 in pregnant swine resulted in many genomic changes. All isolates of porcine origin shared 32 nucleotide and 12 amino acid differences with the virus inoculum AU526. These changes were detected after a single passage in pregnant swine and were conserved during the subsequent five passages. Amino acid changes occurred primarily in genomic regions encoding the BVDV structural proteins E2 and E rns . These results suggest that BVDV infections in pregnant swine may contribute significantly to the genetic variability of BVDV and lead to the appearance of adaptive changes., (Copyright © 2020 Kuca, Passler, Newcomer, Neill, Galik, Riddell, Zhang, Bayles and Walz.)

Bovine viral diarrhea virus (BVDV) is an important viral cause of reproductive disease, immune suppression and clinical disease in cattle. The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. BVDV negative beef heifers and cows (n = 122) were randomly assigned to one of four groups. Groups A-C (n = 34/group) received two pre-breeding doses of one of three commercially available multivalent vaccines containing inactivated fractions of BVDV 1 and BVDV 2, and Group D (n = 20) served as negative control and received two doses of saline prior to breeding. Animals were bred, and following pregnancy diagnosis, 110 cattle [Group A (n = 31); Group B (n = 32); Group C (n = 31); Group D (n = 16)] were subjected to a 28-day exposure to cattle persistently infected (PI) with BVDV (1a, 1b and 2a). Of the 110 pregnancies, 6 pregnancies resulted in fetal resorption with no material for testing. From the resultant 104 pregnancies, BVDV transplacental infections were demonstrated in 73 pregnancies. The BVDV fetal infection rate (FI) was calculated at 13/30 (43%) for Group A cows, 27/29 (93%) for Group B cows, 18/30 (60%) for Group C cows, and 15/15 (100%) for Group D cows. Statistical differences were observed between groups with respect to post-vaccination antibody titers, presence and duration of viremia in pregnant cattle, and fetal infection rates in offspring from BVDV-exposed cows. Group A vaccination resulted in significant protection against BVDV infection as compared to all other groups based upon outcome measurements, while Group B vaccination did not differ in protection against BVDV infection from control Group D. Ability of inactivated BVDV vaccines to provide protection against BVDV fetal infection varies significantly among commercially available products; however, in this challenge model, the inactivated vaccines provided unacceptable levels of BVDV FI protection., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bovine viral diarrhea virus (BVDV) is an economically important pathogen of cattle that can also infect a wide range of domestic and wild species including sheep, goats, deer, camelids, and pigs. BVDV isolates are genetically highly diverse and previous work demonstrated that many substitutions were introduced in the viral genome during acute infections in cattle. In contrast, only limited information exists regarding changes occurring during BVDV infections in species other than cattle. The purpose of this study was to determine the changes introduced in the open reading frame (ORF) of the BVDV genome during serial infection of pregnant cattle and sheep with an isolate of bovine origin. Serial experimental inoculations were performed in six pregnant heifers and six pregnant ewes using BVDV-1b isolate AU526 in the first heifer and ewe, and serum from the preceding acutely infected dam thereafter. Complete ORF sequences were determined for 23 BVDV-1b isolates including AU526, one isolate from each pregnant dam, and one isolate from each BVDV-positive offspring born to these dams. Sequence comparison revealed that greater numbers of substitutions occurred during serial infection of pregnant sheep than of pregnant cattle. Furthermore, multiple host-specific amino acid changes were gradually introduced and conserved. These changes were more abundant in ovine isolates and occurred primarily in the E2 coding region. These results suggest that BVDV infections in heterologous species may serve as a significant source of viral genetic diversity and may be associated with adaptive changes.

We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values <25 were observed in group 1 calves from PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

Bovine viral diarrhea virus (BVDV) is responsible for significant losses to the cattle industry. Currently, modified-live viral (MLV) and inactivated viral vaccines are available against BVDV, often in combination with other viral and bacterial antigens. Inactivated and MLV vaccines provide cattle producers and veterinarians safe and efficacious options for herd immunization to limit disease associated with BVDV infection. Vaccination of young cattle against BVDV is motivated by prevention of clinical disease and limiting viral spread to susceptible animals. For reproductive-age cattle, vaccination to prevent viremia and birth of persistently infected offspring is considered more important, while also more difficult to achieve than prevention of clinical disease. Recent advances have been made in the understanding of BVDV vaccine efficacy. In terms of preventing clinical disease, current BVDV vaccines have been demonstrated to have a rapid onset of immunity and MLV vaccines can be effectively utilized in calves possessing maternal immunity. For reproductive protection, more recent studies using multivalent MLV vaccines have demonstrated consistent fetal protection rates in the range of 85-100% in experimental studies. Proper timing and administration of BVDV vaccines can be utilized to maximize vaccine efficacy to provide an important contribution to reducing risks associated with BVDV infection. With improvements in vaccine formulations and increased understanding of the protective immune response following vaccination, control of BVDV through vaccination can be enhanced., (Copyright © 2017. Published by Elsevier B.V.)

Bovine herpesvirus 1 is ubiquitous in cattle populations and is the cause of several clinical syndromes including respiratory disease, genital disease, and late-term abortions. Control of the virus in many parts of the world is achieved primarily through vaccination with either inactivated or modified-live viral vaccines. The purpose of this meta-analysis was to determine the cumulative efficacy of BoHV-1 vaccination to prevent abortion in pregnant cattle. Germane articles for inclusion in the analysis were identified through four online scientific databases and the examination of three review and ten primary study article reference lists. A total of 15 studies in 10 manuscripts involving over 7500 animals were included in the meta-analysis. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of vaccination. Subgroup analyses were performed based on type of vaccine, MLV or inactivated, and the type of disease challenge, experimentally induced compared to field studies. A 60% decrease in abortion risk in vaccinated cattle was demonstrated. The greatest decrease in abortion risk was seen in studies with intentional viral challenge although vaccination also decreased abortion risk in field studies. Both inactivated and modified-live viral vaccines decreased abortion risk. This meta-analysis provides quantitative support for the benefit of bovine herpesvirus 1 vaccination in the prevention of abortion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

OBJECTIVE To determine titers of serum antibodies against 3 genotypes of bovine parainfluenza 3 virus (BPI3V) in unvaccinated ungulates in Alabama. ANIMALS 62 cattle, goats, and New World camelids from 5 distinct herds and 21 captured white-tailed deer. PROCEDURES Serum samples were obtained from all animals for determination of anti-BPI3V antibody titers, which were measured by virus neutralization assays that used indicator (reference) viruses from each of the 3 BPI3V genotypes (BPI3V-A, BPI3V-B, and BPI3V-C). The reference strains were recent clinical isolates from US cattle. Each sample was assayed in triplicate for each genotype. Animals with a mean antibody titer ≤ 2 for a particular genotype were considered seronegative for that genotype. RESULTS Animals seropositive for antibodies against BPI3V were identified in 2 of 3 groups of cattle and the group of New World camelids. The geometric mean antibody titer against BPI3V-B was significantly greater than that for BPI3V-A and BPI3V-C in all 3 groups. All goats, captive white-tailed deer, and cattle in the third cattle group were seronegative for all 3 genotypes of the virus. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that BPI3V-A may no longer be the predominant genotype circulating among ungulates in Alabama. This may be clinically relevant because BPI3V is frequently involved in the pathogenesis of bovine respiratory disease complex, current vaccines contain antigens against BPI3V-A only, and the extent of cross-protection among antibodies against the various BPI3V genotypes is unknown.

Both bovine viral diarrhea virus and bovine herpesvirus 1 can have significant negative reproductive impacts on cattle health. Vaccination is the primary control method for the viral pathogens in US cattle herds. Polyvalent, modified-live vaccines are recommended to provide optimal protection against various viral field strains. Of particular importance to bovine viral diarrhea control is the limitation of contact of pregnant cattle with potential viral reservoirs during the critical first 125 days of gestation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The objective of this retrospective study was to characterize the relative prevalence of diagnoses and location of lameness lesions in beef cattle. Medical records from 2005 to 2012 were reviewed and 745 cases of beef cattle that had presented for lameness were identified. Information regarding signalment, lesion location, and cause of lameness was analyzed. The cause of lameness was localized to the foot in approximately 85% of cases; a hind limb was affected over 70% of the time. The lateral claw was most commonly affected in cases of both fore- and hind-limb lameness. The most common diagnoses of noninfectious etiology were screw claw, vertical fissure, and interdigital fibroma. Infectious foot disease accounted for only 20% of foot lameness. Routine foot trimming may be warranted in some herds to improve weight-bearing balance and alleviate lameness.

Objective: To evaluate the efficacy of 4 commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding caused by bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV1) in early-weaned beef calves., Animals: 54 early-weaned beef steers (median age, 95 days)., Procedures: Calves were randomly assigned to 1 of 5 groups and administered PBSS (group A [control]; n = 11) or 1 of 4 commercially available modified-live virus vaccines that contained antigens against BHV1, BVDV types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus (groups B [11], C [10], D [11], and E [11]). Forty-five days after vaccination, calves were exposed simultaneously to 6 cattle persistently infected with BVDV and 8 calves acutely infected with BHV1 for 28 days (challenge exposure). For each calf, serum antibody titers against BVDV and BHV1 were determined before vaccination and before and after challenge exposure. Virus isolation was performed on nasal secretions, serum, and WBCs at predetermined times during the 28-day challenge exposure., Results: None of the calves developed severe clinical disease or died. Mean serum anti-BHV1 antibody titers did not differ significantly among the treatment groups at any time and gradually declined during the study. Mean serum anti-BVDV antibody titers appeared to be negatively associated with the incidence of viremia and BVDV shedding. The unvaccinated group (A) had the lowest mean serum anti-BVDV antibody titers. The mean serum anti-BVDV antibody titers for group D were generally lower than those for groups B, C, and E., Conclusions and Clinical Relevance: Results indicated differences in vaccine efficacy for the prevention of BVDV viremia and shedding in early-weaned beef calves.

Cerebellar abiotrophies, also known as cerebellar ataxias, are characterized by premature post-natal degeneration of cerebellar neurons. This report describes the clinical, magnetic resonance imaging (MRI), gross, histopathological and immunohistochemical features of a novel inherited cerebellar abiotrophy in a cohort of three closely related mixed-breed goats (Capra aegagrus hircus) in the southeastern USA. The animals all presented with early juvenile-onset ataxia, hypermetria, wide-based stance, head tremors and nystagmus. On MRI and at gross examination, there was moderate thinning of the cerebellar vermis and sharpening of the folia. Histologically, the vermis, paravermis and flocculonodular lobe had moderate to severe segmental loss of Purkinje cells with sparing of the hemispheres and secondary loss of granule cells and astrogliosis. Heritable cerebellar ataxias have been reported in many domestic animal species, but not, to the authors' knowledge, as a heritable condition in goats., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Programs for control and eradication of bovine viral diarrhea virus (BVDV) are often considered prudent when the expense of a control program within a specified time frame effectively prevents loss due to disease and the expense of control does not exceed the costs associated with infection. In some geographic areas, concerns about animal welfare or desires to reduce antibiotic usage may motivate BVDV control even when control programs are associated with a lack of financial return on investment. In other geographic areas, concerns about financial return on investment may be the key motivating factor in considering implementation of BVDV control programs. Past experiences indicate that systematic, well-coordinated control programs have a clear potential for success, while voluntary control programs in cultures of distributed decision-making often result in notable initial progress that ultimately ends in dissolution of efforts. Segmentation of the cattle industry into cow-calf producers, stocker/backgrounders, and feedlot operators amplifies the distribution of decision-making regarding control programs and may result in control measures for one industry segment that are associated with significant costs and limited rewards. Though the host range of BVDV extends well beyond cattle, multiple eradication programs that focus only on testing and removal of persistently infected (PI) cattle have proven to be effective in various countries. While some individuals consider education of producers to be sufficient to stimulate eradication of BVDV, research surrounding the adoption of innovative health care procedures suggests that the process of adopting BVDV control programs has a social element. Collegial interactions and discussions may be crucial in facilitating the systematic implementation necessary to optimize the long-term success of control programs. Compulsory control programs may be considered efficient and effective in some regions; however, in a nation where individual identification of cattle remains voluntary, the likelihood of effective compulsion to control BVDV within a farm or ranch appears to be very unlikely. While currently available diagnostic tests are sufficient to support BVDV eradication via systematic, well-coordinated programs, the development of a diagnostic procedure to safely and consistently detect the gestation of a PI fetus after 5 months of gestation would be a valuable research breakthrough. This desired testing modality would allow diagnosis of PI calves, while the dam continues to provide biocontainment of the infected fetus. This development could speed the progress of control programs in achieving the goal of BVDV control and eventual eradication.

Bovine viral diarrhea virus (BVDV) is an important reproductive pathogen of cattle worldwide. The reproductive outcome of BVDV infection is largely dependent on the immune status of the dam and the stage of gestation at the time of infection. Potential sequelae include failure of conception, abortion, a variety of congenital malformations, and fetal infection. Vaccination is a possible tool in the control of BVDV, and there has been a recently renewed focus on providing fetal protection through vaccination. Consequently, the aim of this study was to evaluate the efficacy of BVDV vaccination to prevent reproductive disease by performing a quantitative synthesis of previously published studies. Pertinent articles to be included in the analysis were identified by performing a search in four relevant scientific databases (PubMed, CAB abstracts, National Agricultural Library catalog, and Web of Science) and examining the reference lists of 10 germane review articles. Inclusion criteria for the meta-analysis mandated that the studies were controlled, primary studies that included necessary data for use in the meta-analysis (e.g., group size, number of abortions). Forty-six studies in 41 separate articles matched the inclusion criteria. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of BVDV vaccination on three outcomes: risk of fetal infection, abortion risk, and pregnancy risk. Within each outcome, subanalyses were performed to evaluate the effect of a variety of interventions, including modified live, inactivated, polyvalent and monovalent vaccination, homologous, heterologous, or field challenge, and studies with only bovine subjects. The analysis revealed a decrease in abortions of nearly 45% and a nearly 85% decrease in fetal infection rate in cattle vaccinated for BVDV compared with unvaccinated cohorts. Additionally, pregnancy risk was increased by approximately 5% in field trials of BVDV vaccinates. This meta-analysis provides quantitative support for the benefit of vaccination in the prevention of BVDV-associated reproductive disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recently, in the United States, a dairy bull was diagnosed as the second confirmed case of persistent testicular infection (PTI) with bovine viral diarrhea virus (BVDV). The first objective of this study was to evaluate the testing methodologies currently used by the artificial insemination industry in order to improve the detection of bulls with PTI. This study evaluated the impact of multiple factors ([1] sample tested, [2] sample handling, [3] assay used, and [4] assay methodology) on the sensitivity of detection of BVDV. The second objective of this study was to evaluate the transmissibility of BVDV from the bull through casual or sexual contact. Results from this study indicate that straws of semen should be transported to the diagnostic laboratory in liquid nitrogen dry shippers. PCR proved to be a more sensitive assay than virus isolation; however, certain PCR protocols exhibited greater diagnostic sensitivity than others. Insemination with cryopreserved semen from this infected bull caused viral transmission to a seronegative heifer resulting in viremia and seroconversion. After 42 months of age, the bull appeared to clear the infection. In conclusion, this bull validates that natural exposure to a 1a strain of BVDV can result in a unique PTI causing contamination of semen with detectable infectious virus. Appropriate handling and testing of samples is necessary in order to detect bulls exhibiting PTI. Additionally, PTI with BVDV may potentially be cleared after an extended duration., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Viral disease is one of the major causes of financial loss and animal suffering in today's cattle industry. Increases in global commerce and average herd size, urbanization, vertical integration within the industry and alterations in global climate patterns have allowed the spread of pathogenic viruses, or the introduction of new viral species, into regions previously free of such pathogens, creating the potential for widespread morbidity and mortality in naïve cattle populations. Despite this, no antiviral products are currently commercially licensed for use in bovine medicine, although significant progress has been made in the development of antivirals for use against bovine viral diarrhea virus (BVDV), foot and mouth disease virus (FMDV) and bovine herpesvirus (BHV). BVDV is extensively studied as a model virus for human antiviral studies. Consequently, many compounds with efficacy have been identified and a few have been successfully used to prevent infection in vivo although commercial development is still lacking. FMDV is also the subject of extensive antiviral testing due to the importance of outbreak containment for maintenance of export markets. Thirdly, BHV presents an attractive target for antiviral development due to its worldwide presence. Antiviral studies for other bovine viral pathogens are largely limited to preliminary studies. This review summarizes the current state of knowledge of antiviral compounds against several key bovine pathogens and the potential for commercial antiviral applications in the prevention and control of several selected bovine diseases.

The pestiviruses, bovine viral diarrhea virus (BVDV), classical swine fever (CSFV) and border disease virus, are important livestock pathogens in many countries, but current vaccines do not completely prevent the spread of infection. Control of pestiviral diseases is especially difficult due to the constant viremia and viral shedding of persistently infected (PI) animals, which must be identified and eliminated to prevent disease transmission. Existing vaccines are limited by the delay between vaccination and the onset of protection, the difficulty of differentiating serologically between vaccinated and naturally infected animals and the need for broad vaccine cross-protection against diverse virus strains. Antiviral therapy could potentially supplement vaccination by providing immediate protection in the case of an outbreak. Numerous compounds with in vitro antiviral activity against BVDV have been identified through its role as a surrogate for hepatitis C virus. Fewer drugs active against CSFV have been identified, but many compounds that are effective against BVDV will likely inhibit CSFV, given their similar genomic sequences. While in vitro research has been promising, the paucity of efficacy studies in animals has hindered the commercial development of effective antiviral drugs against the pestiviruses. In this article, we summarize the clinical syndromes and routes of transmission of BVD, CSF and border disease, discuss currently approved vaccines, review efforts to develop antiviral therapies for use in outbreak control and suggest promising directions for future research., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen capable of causing disease affecting multiple body systems. Previous studies have shown 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) effectively prevents BVDV infection in cell culture. The aim of this project was to assess the efficacy of DB772 for the prevention of acute BVDV infection. Four calves seronegative to BVDV were treated with DB772 and another 4 calves were treated with diluent only on the same dosing schedule. Each calf was subsequently challenged intranasally with BVDV. Virus was isolated consistently from untreated calves on days 4 to 8, while treated calves remained negative by virus isolation during this period. Azotemia was exhibited by all treated calves on day 4 resulting in the euthanasia of 1 calf on day 10 and the death of another on day 13. Virus was isolated from the 2 remaining treated calves on day 14 or 21. On day 21, both remaining treated calves and all 4 untreated calves had anti-BVDV antibody titers > 1:2048. This pilot study indicates that DB772 temporarily prevented acute disease due to BVDV, but carries a significant concern of renal toxicity.

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen for which there is no specific therapeutic agent. A previous study using 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) to treat calves persistently infected with BVDV resulted in a decrease in the viral load of infected calves but treatment resulted in the rapid selection of drug-resistant mutant isolates. In this article we describe three mutations found in the mutant isolates associated with in vivo and in vitro resistance to DB772. All three mutations are found in the NS5B which functions as the RNA-dependent-RNA-polymerase during viral replication. Growth curves for the mutant isolates were not largely different from those of wild-type isolates when cultured in the absence of DB772. Thus, DB772 appears to act by binding to the specified domain but binding is disrupted or inhibited by the described mutation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Pestiviruses are economically important pathogens of livestock. An aromatic cationic compound (DB772) has previously been shown to inhibit bovine viral diarrhea virus (BVDV) type 1 in vitro at concentrations lacking cytotoxic side effects. The aim of this study was to determine the scope of antiviral activity of DB772 among diverse pestiviruses. Isolates of BVDV 2, border disease virus (BDV), HoBi virus, pronghorn virus and Bungowannah virus were tested for in vitro susceptibility to DB772 by incubating infected cells in medium containing 0, 0.006, 0.01, 0.02, 0.05, 0.1, 0.2, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5 or 25μM DB772. The samples were assayed for the presence of virus by virus isolation and titration (BDV and BVDV 2) or PCR (HoBi, pronghorn and Bungowannah viruses). Cytotoxicity of the compound was assayed for each cell type. Complete inhibition of BVDV 2, BDV, and Pronghorn virus was detected when DB772 was included in the culture media at concentrations of 0.20μM and higher. In two of three tests, a concentration of 0.05μM DB772 was sufficient to completely inhibit HoBi virus replication. Bungowannah virus was completely inhibited at a concentration of 0.01μM DB772. Thus, DB772 effectively inhibits all pestiviruses studied at concentrations >0.20μM. As cytotoxicity is not evident at these concentrations, this antiviral compound potentially represents an effective preventative or therapeutic for diverse pestiviruses., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Bovine viral diarrhea virus (BVDV) strains circulating in livestock herds show significant sequence variation. Conventional wisdom states that most sequence variation arises during acute infections in response to immune or other environmental pressures. A recent study showed that more nucleotide changes were introduced into the BVDV genomic RNA during the establishment of a single fetal persistent infection than following a series of acute infections of naïve cattle. However, it was not known if nucleotide changes were introduce when the virus crossed the placenta and infected the fetus or during the acute infection of the dam., Methods: The sequence of the open reading frame (ORF) from viruses isolated from four acutely infected pregnant heifers following exposure to persistently infected (PI) calves was compared to the sequences of the virus from the progenitor PI calf and the virus from the resulting progeny PI calf to determine when genetic change was introduced. This was compared to genetic change found in viruses isolated from a pregnant PI cow and its PI calf, and in three viruses isolated from acutely infected, non-pregnant cattle exposed to PI calves., Results: Most genetic changes previously identified between the progenitor and progeny PI viruses were in place in the acute phase viruses isolated from the dams six days post-exposure to the progenitor PI calf. Additionally, each progeny PI virus had two to three unique nucleotide substitutions that were introduced in crossing the placenta and infection of the fetus. The nucleotide sequence of two acute phase viruses isolated from steers exposed to PI calves revealed that six and seven nucleotide changes were introduced during the acute infection. The sequence of the BVDV-2 virus isolated from an acute infection of a PI calf (BVDV-1a) co-housed with a BVDV-2 PI calf had ten nucleotides that were different from the progenitor PI virus. Finally, twenty nucleotide changes were identified in the PI virus of a calf born to a PI dam., Conclusions: These results demonstrate that nucleotide changes are introduced into the BVDV infecting pregnant cattle at rates of 2.3 to 8 fold higher then during the acute infection of non-pregnant animals.

Background: Animals persistently infected (PI) with bovine viral diarrhoea virus (BVDV) are a key source of viral propagation within and among herds. Currently, no specific therapy exists to treat PI animals. The purpose of this research was to initiate evaluation of the pharmacokinetic and safety data of a novel antiviral agent in BVDV-free calves and to assess the antiviral efficacy of the same agent in PI calves., Methods: One BVDV-free calf was treated with 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) once at a dose of 1.6 mg/kg intravenously and one BVDV-free calf was treated three times a day for 6 days at 9.5 mg/kg intravenously. Subsequently, four PI calves were treated intravenously with 12 mg/kg DB772 three times a day for 6 days and two PI control calves were treated with an equivalent volume of diluent only., Results: Prior to antiviral treatment, the virus isolated from each calf was susceptible to DB772 in vitro. The antiviral treatment effectively inhibited virus for 14 days in one calf and at least 3 days in three calves. Subsequent virus isolated from the three calves was resistant to DB772 in vitro. No adverse effects of DB772 administration were detected., Conclusions: Results demonstrate that DB772 administration is safe and exhibits antiviral properties in PI calves while facilitating the rapid development of viral resistance to this novel therapeutic agent., (© 2012 International Medical Press)

Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle with a high degree of sequence diversity amongst strains circulating in livestock herds. The driving force behind change in sequence is not well established but the inaccurate replication of the genomic RNA by a viral RNA polymerase without proof-reading capabilities as well as immune pressure on immunodominant proteins are thought to play major roles. Additionally, it is not clear when the majority of changes are introduced, whether during acute infections with exposure to innate and adaptive immune responses or in establishment of persistent infections (PI) in utero. To examine which generates greater sequence diversity, two groups of viruses were compared. The first was six isolates of a single strain of BVDV-2 that were isolated over greater than a year's time. These viruses caused a series of severe acute (SA) BVD outbreaks over a large geographic area. Changes in nucleotide sequence were determined by comparison of the sequence of each strain to the six virus consensus sequence. The second group was composed of six BVDV strains isolated from PI calves whose dams were exposed to PI cattle. Changes were identified by comparison of the sequence of the progenitor PI virus to that of the progeny viruses from the single in vivo 'passage'. The open reading frames (ORF) of the six SA isolates were >99% identical at the nucleotide level with 30% of the changes being nonsynonymous changes. The amount of genetic change increased with time and distance from the original outbreak. Similarly, the PI viruses isolated from single passage PI calves had >99% identity with the progenitor virus. The number of nucleotide changes in these viruses was equal to or greater than that observed in the SA viruses. The majority of the nonsynonymous changes were found in the structural proteins, with 65% of these occurring in the immunodominant E2 protein. Antigenic mapping studies using a monoclonal antibody panel specific for the BVDV E2 protein showed no antigenic differences amongst the six SA viruses, nor between the progenitor and progeny type 1a and type 2 persistent viruses. However, antigenic differences were observed in the two type 1b progeny viruses that possessed the greatest number of amino acid changes. Two antibodies were found to have altered staining patterns. These results suggest that the establishment of a single persistent infection results in more rapid generation of genetic diversity in BVDV strains than a series of acute infections and may contribute to antigenic change in the absence of an immune response., (Published by Elsevier B.V.)