Bovine herpesvirus type 4: a special herpesvirus (review article)

This paper summarizes the history of and information on bovine herpesvirus type 4 (BoHV-4) from the first isolation to the most recent results. For almost twenty years BoHV-4 has been considered a typical herpes 'orphan' virus, which infects several species but causes no illness. The latest experiments revealed the close relationship of this virus with the immune system and other tissues. The virus was even considered as a possible candidate for a vector vaccine. BoHV-4 as a strange herpesvirus has several features which are not characteristic of other herpesviruses, such as several latency sites, persistence in serum, dividing cells necessary for virus replication, and the wide host range. In addition to describing the main features of the virion, replication, clinical signs, nomenclature problems, this review intends to concentrate on the new and strange results coming out from several laboratories worldwide. It is also suggested that because the virus combines several properties of various herpesvirus subfamilies and because of its close relationship with the immune system, it may deserve further attention as a representative of a potentially new genus within the Gammaherpesvirinae subfamily.     

Bovine herpesvirus 1 glycoprotein D expression in bovine upper respiratory tract mediated by a human adenovirus type 5

Bovine herpesvirus 1 glycoprotein D (gD) gene expression by recombinant replication defective human adenovirus type 5 (HAdV-5) was investigated in calves using indirect immunofluorescence microscopy (IIFM), confocal laser scanning microscopy (CLSM) and RT-PCR. One fold intranasal instillation of HAdV-5-expressing gD in the cattle upper respiratory tract showed a short term expression of at least 5 days, but not 10 days, limited only to epithelial cells localised in the epithelium of the nasal mucosa in one out of six calves. Observed limited gene transfer into well differentiated cattle airway epithelial cells must be taken into consideration in order to enhance transfection efficiency, and consequently the vaccine potential of this vector.     

Present and future of veterinary viral vaccinology: a review

This review deals briefly with some key developments in veterinary vaccinology, lists the types of vaccines that are used for vaccinations commonly performed in food animals as well as in companion animals, and indicates that the practising veterinarian can select the best vaccine by comparing the results of efficacy studies. Diva (Differentiating Infected from Vaccinated Animals; also termed marker) vaccines and companion diagnostic tests have been developed that can be used for progammes aimed to control or eradicate virus infections. Vaccine-induced herd immunity, which can be measured relatively easily when diva vaccines are used, is a crucial issue in such programmes. Current vaccine research follows many routes towards novel vaccines, which can be divided into non-replicating ('killed') and replicating ('live') vaccines. Promising trends are the development of DNA vaccination, vector vaccines, and attenuation of DNA and RNA viruses by DNA technology. The lack of (in vitro) correlates of vaccine protection markedly hampers progress in vaccine research. Various characteristics of an 'ideal' vaccine are listed, such as multivalency and the induction of lifelong immunity after one non-invasive administration in animals with maternal immunity. Future research should be aimed at developing vaccines that approach the ideal as closely as possible and which are directed against diseases not yet controlled by vaccination and against newly emerging diseases.     

Bovine ephemeral fever: a review

Bovine ephemeral fever is a viral disease of cattle and buffaloes besides subclinical involvement of a variety of ruminant species. The subtropical and temperate regions of Africa, Asia and Australia have experienced the major epidemic of the bovine ephemeral fever but the occurrence in the tropics can not be overlooked. Although the substantial role played by the vectors viz., mosquitoes and culicoides in bovine ephemeral fever perpetuation and dissemination, other vector involvement if any should be extensively studied. The clinical severity of the disease is not apparent and the mortality is low. However, high morbidity, enormous economic losses in terms of significant reduction in production, disruption of national and international trade and finally a variety of complications resulting from the disease have drawn appreciable attention from the researchers around the world to resolve the unsolved questions in this area. In this review, detailed informations of all the aspects of the disease has been provided in a simple, lucid and easily understandable manner.     

Bovine spongiform encephalopathy: a review

Transmissible Spongiform Encephalopathies are a group of chronic, always fatal diseases affecting the central nervous system of humans and animals. They occur in all species and are probably caused by agents called prions. In this minireview, a first part provides an overview of the various disease forms, a second part is devoted to the molecular biology of transmissible spongiform encephalopathies, and a last part deals with the specific problems of the Bovine Spongiform Encephalopathy.     

Bovine leucocyte adhesion deficiency: A review of a modern disease and its implications

Bovine leucocyte adhesion deficiency (BLAD) is a genetic disease of cattle which affects the hematopoietic system. In the last decade BLAD has become a disease of economic importance in the dairy industry. This review describes the chronological developments and thinking that led to the elucidation of BLAD as a disease distinct from previous models in canine and human populations. All species affected show signs of chronic and recurrent infections. Necrotic and/or gangrenous infections of soft tissues are prevalent, in addition to secondary infections with bacteria or fungi. Low birthweight and unthriftiness are key signs in all species affected by leucocyte adhesion deficiency (LAD). Dermatomycoses and impaired pus formation are also common findings. The physiological basis for BLAD is a deficiency in the chemotactic and phagocytic properties of leucocytes and particularly neutrophils. The inhibition of diapedesis in the inflammatory response prevents normal immune reactions to invading pathogens. Chronic infections are a consequence of the faulty immune mechanisms. The biochemical aetiology of BLAD involves cell surface glycoprotein molecules known as integrins. These are responsible for the cell-cell interactions necessary for neutrophils to adhere to vascular endothelium in a normal individual. Experiments with monoclonal antibodies to block LFA-1, Mac-1, and p150,95 (three integrins vital for cell-cell interactions) mimic BLAD symptomatology and have led to the discovery of the reciprocal intercellular adhesion molecule (ICAM). Through pedigree analysis and biochemical detection with restrictive endonucleases, BLAD has been isolated genetically to a single gene locus. The economic significance and prophylaxis of the disease are briefly discussed. In addition, the beneficial aspects of the study of BLAD are considered. There are advantages in producing a BLAD-like state for preventing transplant rejection, ischaemia-reperfusion injury and other problems arising from the deleterious effects of the inflammatory response.     

Bovine herpesvirus 4 isolates: a comparison of three major glycoproteins.

Twenty-four Belgian field isolates of bovine herpesvirus 4 (BHV-4), together with four reference strains were compared by radio-immunoprecipitation and western blotting using a polyvalent antiserum and monoclonal antibodies raised against major glycoproteins. Most of these strains showed the same protein profile as the European reference strain Movar 33/63. For two strains the molecular weight of gp 6, p (gp 10/gp 17) and gp 10 were the same as those of the American reference strain DN 599. No relationship could be established between the protein profiles and origin of the isolates or with the restriction patterns. This study provides a view of the molecular weight variations of the major BHV-4 glycoproteins among field isolates.     

Characterization of the glycoprotein D gene products of equine herpesvirus 1 using a prokaryotic cell expression vector

The gene encoding equine herpesvirus 1 (equine abortion virus; EHV-1) glycoprotein D was engineered into the prokaryotic vector pEX, and expressed as a β-galactosidase fusion product, which was recognized by pooled equine sera and anti-EHV-1 rabbit sera. Antibodies raised against the EHV-1 gD fusion product identified strong bands in infected cells at 66 and 68 K and at 138 K in purified virus, thus characterizing the several forms of this major envelope glycoprotein which is an important candidate for inclusion in subunit vaccines.     

Bovine sole ulcer: a literature review

Sole ulcers are the most frequently encountered lesion in lame cattle. They are of growing concern to the dairy industry since the incidence of ulcers is increasing. Ulcers cause financial losses, the animal's wellbeing is disturbed to a high degree and they harm the image of the industry in general. Biomechanic factors and laminitis are of particular significance in the pathogenesis of the sole ulcer. The development of sole contusions and ulcers is assumed to occur in 3 phases (Sinking theory). In the first phase there is a general disturbance in the vascular system of the corium. The second phase follows when the structures that suspend the claw bone within the horn shoe give way. The locus minoris resistentiae has yet to be identified. The claw bone sinks and causes various lesions when it pinches the underlying sole or heel corium. The third phase begins when haemorrhages become visible on the horn surface of the sole or when the sole ulcerates; socalled third phase lesions. The relationship between the development of sole ulcers and anatomical structures such as the claw bone's tuberculum flexorium or the fat bodies under the bone are unclear. Epidemiological studies have shown that sole ulcers have a high rate of recurrence. The healing processes and the factors that influence them have hitherto not been studied.     

Bovine uterine defense mechanisms: a review

Bovine uterine defense mechanisms during physiological and pathological conditions have been reviewed in this article. The initial uterine defense against bacterial infection is phagocytosis by uterine leucocytes (mainly neutrophils). The reported literature showed that very little work has been done on immunoglobulins and their role in the bovine uterine defense mechanisms; however, some investigators have found a positive correlation between gamma-globulin and the development of uterine infection after calving. Many explanations exist for the difference in susceptibility of the uterus to infection during the different phases of estrous cycle; however, most of the reports agreed that the uterine defense mechanism is inadequate during diestrus. The abnormal puerperium effects uterine defense mechanisms adversely and prolongs the time to complete uterine involution. Future treatment may utilise natural antimicrobial substances such as proteins or peptides derived from PMN, chemoattractant substances such as E. coli lipopolysaccharide or a bacteria-free filtrate of streptococci. Specific hyperimmunserum could also be used as opsonin for refractory cases of uterine bacterial infections.     

Bovine herpesvirus 4-associated postpartum metritis in a Spanish dairy herd

In more than 10 Spanish dairy cows, a bovine herpesvirus 4 (BHV4) associated postpartum metritis was confirmed by virus isolation, BHV4-glycoprotein B (gB) PCR and/or serology. In this study, 12 cows with, and, at the time of sampling, 3 cows without clinical signs of acute postpartum metritis from one large dairy herd in Spain were examined for bacterial and viral infections. Blood, placenta/caruncles and uterine contents were collected between day 1 and day 20 post-calving, and examined for the presence of bacteria and for viruses by virus isolation, BHV4 DNA by BHV4-gB PCR and/or BHV4 antibody titres. Bovine herpesvirus 4 was detected in 83% of the cases with clinical signs of acute postpartum metritis by virus isolation and/or BHV4-gB PCR. An increase of BHV4 antibodies was detected in all examined postpartum metritis cows and in the 3 cows without clinical metritis. Two of these 3 cows developed severe metritis a few dayss after collecting the first blood sample. A concurrent infections of BHV4 and bacteria, mainly Arcanobacterium pyogenes and Streptococcus sp., were detected in 73% of the examined uterine contents collected from postpartum metritis affected cows. This case-report study showed a clear association between BHV4 infections and acute postpartum metritis in dairy cows. In addition, the BHV4-associated postpartum metritis appeared to be an emerging syndrome in this Spanish herd.     

Serum antibody responses to equine herpesvirus 1 glycoprotein D in horses, pregnant mares and young foals

The envelope glycoprotein D of equine herpesvirus 1 (EHV-1 gD) has been shown in laboratory animal models to elicit protective immune responses against EHV-1 challenge, and hence is a potential vaccine antigen. Here we report that intramuscular inoculation of EHV-1 gD produced by a recombinant baculovirus and formulated with the adjuvant Iscomatrix elicited virus-neutralizing antibody and gD-specific ELISA antibody in the serum of over 90% of adult mixed breed horses. The virus-neutralizing antibody responses to EHV-1 gD were similar to those observed after inoculation with a commercially available killed EHV-1/4 whole virus vaccine. Intramuscular inoculation of EHV-1 gD DNA encoded in a mammalian expression vector was less effective in inducing antibody responses when administered as the sole immunogen, but inoculation with EHV-1 gD DNA followed by recombinant EHV-1 gD induced increased gD ELISA and virus-neutralizing antibody titres in six out of seven horses. However, these titres were not higher than those induced by either EHV-1 gD or the whole virus vaccine. Isotype analysis revealed elevated gD-specific equine IgGa and IgGb relative to IgGc, IgG(T) and IgA in horses inoculated with EHV-1 gD or with the whole virus vaccine. Following inoculation of pregnant mares with EHV-1 gD, their foals had significantly higher levels of colostrally derived anti-gD antibody than foals out of uninoculated mares. The EHV-1 gD preparation did not induce a significant mean antibody response in neonatal foals following inoculation at 12 h post-partum and at 30 days of age, irrespective of the antibody status of the mare. The ability of EHV-1 gD to evoke comparable neutralizing antibody responses in horses to those of a whole virus vaccine confirms EHV-1 gD as a promising candidate for inclusion in subunit vaccines against EHV-1.     

Bovine postparturient hemoglobinuria: a review of the literature

Predisposing causes of bovine post-parturient hemoglobinuria are summarized along with suspected pathogeneses, clinical signs, laboratory findings, clinical management and early experimentation.     

Equine herpesvirus 1 glycoprotein D expressed in E. coli provides partial protection against equine herpesvirus infection in mice and elicits virus-neutralizing antibodies in the horse

The envelope glycoprotein D of EHV-1 (EHV-1 gD) is essential for virus infectivity and entry of virus into cells and is a potent inducer of virus-neutralizing antibody. In this study, truncated EHV-1 gD (gDt) was expressed with a C-terminal hexahistidine tag in E. coli using a pET vector. Western blot analysis using an anti-gD monoclonal antibody demonstrated the presence of gDt bands at 37.5, 36, 29.5 and 28 kDa. The immunogenicity and protective efficacy of partially purified gDt was compared with gD expressed in insect cells by a recombinant baculovirus (Bac gD) using a BALB/c mouse model of EHV-1 respiratory infection. The proteins were also compared in a prime-boost protocol following an initial inoculation with gD DNA. gDt elicited similar levels of gD-specific antibody and neutralizing antibody compared with Bac gD and also provided a similar level of protection against EHV-1 challenge in mice. Inoculation of horses with gDt elicited EHV-1 gD-specific antibodies including virus-neutralizing antibody, suggesting that despite the lack of glycosylation, E. coli may be a useful vehicle for large scale production of EHV-1 gD for vaccine studies.     

Construction and characterization of a glycoprotein E gene-deleted bovine herpesvirus type 1 recombinant

OBJECTIVE: To construct and characterize a recombinant glycoprotein (g)E gene-deleted bovine herpesvirus (BHV) type 1 (BHV-1). PROCEDURE: The BHV-1 gEgene-coding region and the flanking upstream and downstream sequences were cloned. The aforementioned cloned DNA was digested with suitable enzymes to release the amino terminal two thirds of that region, and was ligated to the beta-galactosidase (beta-gal) gene. The resulting plasmid DNA was cotransfected with DNA from full-length, wild-type (WT), BHV-1 Cooper strain of the virus. Recombinant viruses expressing beta-gal (blue plaques) were plaque purified and assayed further by blot hybridization for genetic characterization and by immunoblotting for reactivity against BHV-1 gE peptide-specific rabbit polyclonal antibody. One recombinant virus, gEdelta3.1IBR, was characterized in vitro and in vivo. The ability of the recombinant virus to induce BHV-1 neutralizing antibodies in infected calves was investigated by plaque-reduction tests. RESULTS AND CONCLUSIONS: The gEdelta3.1IBR virus contained a deletion in the viral gE gene-coding sequences where a stable chimeric reporter (beta-gal) gene was inserted. One-step growth kinetics and virus yield of the recombinant and parent viruses were similar, but early after infection, the recombinant virus yield was comparatively less. After intranasal inoculation, the recombinant gEdelta3.1IBR virus replicated in the upper respiratory tract of calves, but the amount of progeny viruses produced was hundredsfold reduced, and duration of virus shedding was shorter. Results of in vivo calf experiments and serum neutralization tests indicated that deleting the gE gene has little effect on inducing neutralizing antibodies against BHV-1, but is sufficient to reduce BHV-1 virulence in calves.     

Isolation of a glycoprotein E-deleted bovine herpesvirus type 1 strain in the field

During a field trial to evaluate the efficacy of repeated vaccinations with bovine herpesvirus type 1 (BHV-1) marker vaccines, a glycoprotein E (gE)-negative BHV-1 strain was isolated from the nasal secretions of two cows, eight months after vaccination with a gE-negative live-attenuated vaccine, initially given intranasally, then intramuscularly. The strain isolated was characterised using immunofluorescence, restriction analysis and PCR. All the techniques used identified the isolated virus as a gE-negative BHV-1 phenotypically and genotypically identical to the Za strain used as a control.