The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.

Mosaic Bovine Viral Diarrhea Virus Antigens Elicit Cross-Protective Immunity in Calves.

Bovine Viral Diarrhea Virus (BVDV) is an important pathogen that plays a significant role in initiating Bovine Respiratory Disease Complex (BRDC) in cattle. The disease causes multi-billion dollar losses globally due to high calf mortality and increased morbidity leading to heavy use of antibiotics. Current commercial vaccines provide limited cross-protection with several drawbacks such as safety, immunosuppression, potential reversion to virulence, and induction of neonatal pancytopenia. This study evaluates two prototype vaccines containing multiple rationally designed recombinant mosaic BVDV antigens for their potential to confer cross-protection against diverse BVDV strains. Genes encoding three novel mosaic antigens, designated E2123, NS2-31, and NS2-32, were designed in silico and expressed in mammalian cells for the formulation of a prototype protein-based vaccine. The mosaic antigens contain highly conserved protective epitopes from BVDV-1a, -1b, and -2, and included unique neutralizing epitopes from disparate strains to broaden coverage. We tested immunogenicity and protective efficacy of Expi293TM-expressed mosaic antigens (293F-E2123, 293F-NS2-31, and 293F-NS2-32), and baculovirus-expressed E2123 (Bac-E2123) mosaic antigen in calves. The Expi293TM-expressed antigen cocktail induced robust BVDV-specific cross-reactive IFN-γ responses, broadly neutralizing antibodies, and following challenge with a BVDV-1b strain, the calves had significantly (p < 0.05) reduced viremia and clinical BVD disease compared to the calves vaccinated with a commercial killed vaccine. The Bac-E2123 antigen was not as effective as the Expi293TM-expressed antigen cocktail, but it protected calves from BVD disease better than the commercial killed vaccine. The findings support feasibility for development of a broadly protective subunit BVDV vaccine for safe and effective management of BRD.

Clinical bovine viral diarrhoea virus infection in Jordan.

A 1-year-old Holstein Friesian heifer was presented for anorexia and acute diarrhoea. The heifer was born and raised at the farm. Bovine viral diarrhoea virus (BVDV) infection was diagnosed using clinical signs and RT-PCR. Clinical BVDV infection has never been reported in Jordan.

Bovine viral diarrhoea eradication and control programmes in Europe.

The economic impact of BVDV infections has led a number of countries in Europe to start eradication or control programmes. While in both cases the primary step is identification and elimination of persistently infected (PI) animals, the strategy applied thereafter is dependent on the density and seroprevalence of the regional cattle population. One of the first countries to design and implement an eradication programme was Sweden in 1993, a country with a relatively low cattle density and no vaccination. For screening, an indirect antibody ELISA for serum, milk and bulk milk samples is being used. The basics of the Swedish model are no vaccination, voluntary participation, and financing of the entire scheme by the subscribing farmers. BVDV-free herds are certified and permanently checked. While in 1993 only about 35% of the herds were seronegative, about 87% were BVDV-free in 2001. The aim of control programmes in high density areas with high seroprevalence is to minimize economic losses by reducing the incidence of PI animals and thereby virus circulation (German model). Participation is voluntary, and parts of the costs are carried by the public animal insurance (Tierseuchenkasse). Screening is performed using an antigen capture ELISA with blood or serum. In Lower Saxony, for example, a herd is declared BVDV unsuspicious if all animals up to 36 months are BVDV antigen negative and the female offspring older than six months is vaccinated twice (an inactivated vaccine is used for basic immunization, and an attenuated live virus vaccine for boosting).

Anti-viral effect of interferon-alpha on bovine viral diarrhea virus.

To get basic information to control persistent virus infection among domestic animals by cytokines, the antiviral activity of four natural human cytokines against bovine viral diarrhea virus (BVDV) was evaluated. Normal bovine peripheral blood mononuclear leukocytes (PBML) and fetal bovine muscular cells (FBMC) were treated with varying doses of human interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta. The antiviral activity in treated cells was measured by the titration of virus infectivity in comparison with non-treated controls. IFN-alpha significantly suppressed virus growth in both PBML and FBMC. The growth of two cytopathogenic and two noncytopathogenic strains was suppressed in the presence of more than 10(3) u/ml of IFN-alpha. Addition of either TNF-alpha or TNF-beta to IFN-alpha did not potentiate the suppressive effect. IFN-alpha also suppressed the replication of BVDV in PBML from cattle persistently infected with BVDV.

Some respiratory and enteric diseases of cattle: an update.

Fibrinous pneumonia caused 40-45% of death losses in cattle shipped into Bruce County, Ontario. Feeding corn silage within the first 2 weeks of arrival increased mortality. Commingling cattle from different sources and keeping more than 110 cattle in a pen were detrimental. While use of antimicrobials in the starter ration was beneficial, prophylactic use of antimicrobials in the water was not. Mortality was directly proportional to morbidity and treatment costs. Vaccinating against any respiratory disease in the first 2 weeks after arrival was detrimental. Delaying vaccination for at least 2 weeks after arrival prevented the negative effects of vaccination in calves fed corn silage. Morbidity in cattle transported by train or truck did not differ. Bovine respiratory syncytial virus causes severe pulmonary edema-emphysema, with high morbidity and variable mortality, in confined calves in the fall and early winter. Death is usually from secondary bacterial pneumonia. Treatment involves use of pyrilamine maleate, dexamethasone and sulfamethazine. Salmonella muenster causes bloody diarrhea, abortion and death in cattle of any age. Treatment is with antibiotics selected by sensitivity tests. Cryptosporidium causes watery diarrhea in 1- to 2-week-old calves; infection is often fatal despite symptomatic treatment. Diagnosis is by identification of oocysts in fecal sugar flotation solution or May-Grünwald-Giemsa-stained fecal smears. Oral sulfamethazine has been used as a prophylactic.

[Virus diarrhea in calves in South Africa]. / Virus diaree in kalwers in suid-afrika.

The importance of diarrhoea in calves is briefly discussed. The role of viruses as primary invaders of the intestinal epithelium is stressed. The pathogenesis and problems encountered in diagnosing virus associated diarrhoea as well as the morphology of rota and coranavirus are discussed. Possible methods of prevention and treatment are briefly mentioned.