Bovine Viral Diarrhea Virus Infection Research Articles

Epigenetic Modifications of White Blood Cell DNA Caused by Transient Fetal Infection with Bovine Viral Diarrhea Virus.

Bovine viral diarrhea virus (BVDV) infections cause USD 1.5-2 billion in losses annually. Maternal BVDV after 150 days of gestation causes transient fetal infection (TI) in which the fetal immune response clears the virus. The impact of fetal TI BVDV infections on postnatal growth and white blood cell (WBC) methylome as an index of epigenetic modifications was examined by inoculating pregnant heifers with noncytopathic type 2 BVDV or media (sham-inoculated controls) on Day 175 of gestation to generate TI (n = 11) and control heifer calves (n = 12). Fetal infection in TI calves was confirmed by virus-neutralizing antibody titers at birth and control calves were seronegative. Both control and TI calves were negative for BVDV RNA in WBCs by RT-PCR. The mean weight of the TI calves was less than that of the controls (p < 0.05). DNA methyl seq analysis of WBC DNA demonstrated 2349 differentially methylated cytosines (p ≤ 0.05) including 1277 hypomethylated cytosines, 1072 hypermethylated cytosines, 84 differentially methylated regions based on CpGs in promoters, and 89 DMRs in islands of TI WBC DNA compared to controls. Fetal BVDV infection during late gestation resulted in epigenomic modifications predicted to affect fetal development and immune pathways, suggesting potential consequences for postnatal growth and health of TI cattle.

Exosomes-mediated transmission of standard bovine viral diarrhea strain OregonC24Va in bovine trophoblast cells

Bovine viral diarrhoea virus (BVDV) can infect cows on days 30-110 of gestation and crossing the placental barrier, resulting in persistently infected (PI) and causing significant economic losses to dairy farming. Bovine placental trophoblast cells (BTCs) are the major cells in the early chorionic tissue of the placenta and play important roles in placental resistance to viral transmission. In this study, we have confirmed that BTCs is among a groups of cell types those could be infected by BVDV in vivo, and BVDV infection stimulates the autophagic responses in BTCs and promotes the release of exosomes. Meanwhile, the exosomes derived from BTCs can be used by BVDV to spread between placental trophoblast cells, and this mode of transmission cannot be blocked by antibodies against the BVDV E2 protein, whereas the replication and spread of BVDV in BTCs can be blocked by inhibiting autophagy and exosomogenesis. Our study provides a theoretical and practical basis for scientific prediction and intervention of reproductive disorders caused by BVDV infection in cows of different gestation periods from a novel perspective.

Establishment and application of a rapid diagnostic method for BVDV and IBRV using recombinase polymerase amplification-lateral flow device.

Bovine Viral Diarrhea Virus (BVDV) and Infectious Bovine Rhinotracheitis Virus (IBRV) are the two most prevalent infectious diseases in cattle. They both can cause persistent infection and immunosuppression, resulting in significant economic losses in the livestock industry. Therefore, rapid detection of early BVDV and IBRV infections is crucial. In this study, a method for the rapid detection of BVDV and IBRV was established by using recombinase polymerase amplification (RPA) combined with lateral flow device (LFD). By optimizing the temperature and time conditions of the RPA reaction, the sensitivity, specificity, and clinical performance were evaluated. The results indicated that the RPA reaction could be completed at 40°C within 25 min. The LOD for BVDV and IBRV by RPA-LFD were 5.1 × 101 copies/μL and 6.65 × 101 copies/μL, respectively, with no cross-reactivity observed with other viruses such as CSFV, BRSV, BPIV3, BRV, and BCoV. Testing of 32 clinical samples showed consistent results between RPA-LFD and qPCR. The RPA-LFD method established in this study can be used for the rapid clinical detection of BVDV and IBRV, which providing a rapid and convenient molecular biology approach for on-site rapid detection and epidemiological investigations. Simultaneously, it offers technical support for the prevention and control of these viruses.

Outbreak of persistently infected heifer calves with bovine viral diarrhea virus subgenotypes 1b and 1d in a BVDV-vaccinated open dairy herd

Bovine viral diarrhea virus (BVDV) infection has a significant economic impact on beef and dairy industries worldwide. Fetal infection with a non-cytopathic strain may lead to the birth of persistently infected (PI) offspring, which is the main event in the epidemiological chain of BVDV infection. This report describes the birth of 99 BVDV-PI heifer calves within 52 days of birth in a regular BVDV-vaccinated Brazilian dairy cattle herd and the subgenotypes of the infecting field strains. This study was conducted in a high-yielding open dairy cattle herd that frequently acquired heifers from neighboring areas for replacement. The farm monitors the birth of PI calves by screening all calves born using an ELISA (IDEXX) for BVDV antigen detection. All calves aged 1–7 days were evaluated. For positive and suspected results, the ELISA was repeated when the calves were close to one month old. A total of 294 heifer calves were evaluated between February and March 2021. Of these, 99 (33.7 %) had positive ELISA results and were considered PI calves. To evaluate the predominant BVDV species and subgenotypes in this outbreak, whole blood samples were collected from 31 calves born during the study period. All samples were submitted to the RT-PCR assay for the partial amplification of the BVDV 5′-UTR region, and these amplicons were subjected to nucleotide sequencing. Phylogenetic analysis identified BVDV-1b and BVDV-1d in 16 and 13 heifer calves, respectively. In two calves, it was not possible to determine the BVDV-1 subgenotype. Detection of PI animals and monitoring of circulating BVDV subgenotype strains are central to disease control. This study shows that regular BVDV vaccination alone may be insufficient to prevent BVDV infection in high-yielding open dairy cattle herds. Other biosecurity measures must be adopted to avoid the purchase of cattle with acute infections by BVDV or BVDV-PI, which can cause a break in the health profile of the herd and economic losses.

Seroprevalence of bovine viral diarrhea virus and detection of persistently infected (PI) animals in dairy farms of Holeta, central Ethiopia

Bovine viral diarrhea virus (BVDV) is one of the most important pathogens of the reproductive systems that have a significant socio economic impact on the dairy industry. A cross-sectional study was conducted on 17 randomly selected farms out of 133 registered dairy farms in Holeta, a town in the Walmera district of Ethiopia. The study aimed to detect BVDV antigen-positive animals and investigate the seroprevalence of BVDV infection. A total of 337 serum samples were collected from selected farms with no history of BVDV vaccination. The indirect enzyme-linked immunosorbent assay (I-ELISA) test was the screening test used to detect antibodies against BVDV. In contrast, antigencapture ELISA was used for the detection of BVDV antigens in seronegative animals. A logistic regression model was used to assess the association between potential predictors and BVDV exposure. The overall animal level seroprevalence was 15.4%, and 64.7% of the herds had at least one seropositive animal. From 285 seronegative animals, one animal (0.4%) was found positive for BVDV antigen. The same animal was found positive in a double check 21 days later. In this study, cows with a history of abortion (OR = 6.3; 95% CI: 1.61 -13.1), history of repeated breeding (OR = 7; 95% CI: 2.5 - 14.3), animals managed intensively (OR = 4.6; 95% CI: 1.6 - 13.0) and multiparous cows (OR = 3.6; 95% CI: 1.5 - 8.9) had higher proportion of seroreactors in their respective comparison category (p&lt;0.05). Besides, cows with a history of congenital defective calve birth (OR = 15.2; 95% CI: 3.2 - 73.6), adult age groups (OR = 2.9; 95% CI: 1.0-7.9), and cows bred both artificially and natural mating (OR = 4.6; 95% CI: 1.7 - 12.6) were statistically associated with BVDV seropositivity (p&lt;0.05). In conclusion, this report demonstrated the presence of persistently infected (PI) dairy cattle in Ethiopia. Thus, the findings warrant the need for immediate control intervention that involves both screening and culling of PI animals and vaccination.

Development and Evaluation of Recombinant NS3 Protein-based ELISA for the Detection of Bovine Viral Diarrhea Virus (BVDV) Antibodies

Background: Bovine Viral Diarrhea (BVD) is an important infectious disease that has a significant economic impact on dairy farms. Early detection of antibodies against BVD virus within herds can help reduce economic losses resulting from impaired animal health and reproductive performance. However, commercial ELISA tests tend to be expensive and unaffordable for smallholder farmers in Thailand. This study aims to develop an in- house indirect ELISA for the detection of antibodies to BVD. Methods: Gene synthesis and codon optimization were performed prior to protein expression. The prepared recombinant NS3 protein was confirmed through western blot analysis. Assay validation involved a comparison with an indirect commercial ELISA using a set of field serum samples (n=497) as references to evaluate its diagnostic accuracy. Measurements for test agreement and assay repeatability were calculated to assess performance. Result: The area under the receiver operating characteristic (ROC) curve was 0.86, indicating good discrimination between BVDV-positive and negative animals. The kappa coefficient, with an identified optimal cut-off value, was 0.577, indicated moderate agreement between the two tests. Additionally, the assay exhibited acceptable repeatability, with coefficients of variations (CVs) of 8.8% and 15.1% for intra-assay and inter-assay variations, respectively. This developed ELISA demonstrates both discriminatory ability and repeatability, making it a valuable alternative tool for the serodiagnosis of BVDV infection, especially in low-resource settings.

Serosurvey and Associated Risk Factors for Bovine Viral Diarrhea Virus Infection in Dromedary Camels in Egypt

Bovine viral diarrhea (BVD) is a disease that affects ruminants globally, including camels, and causing significant financial losses. The epidemiology of BVD in camels in Egypt are not well understood. Thus, this study aimed to determine the prevalence of anti-BVD virus (BVDV) antibodies in camels and identify the potential variables associated with the infection. A total of 400 camel sera from three Egyptian governorates were examined using commercial ELISA kit. The total seroprevalence was 4.8% in examined camels and the BVDV seropositivity were more prevalent in camels from Giza governorate. The highest seropositivity was found in aged camels more than 8 years (OR = 8.62, 95%CI: 1.03–71.87), camels from herd size less than 30 (OR = 4.20, 95%CI: 0.89–19.78), previously aborted animals (OR = 5.98, 95%CI: 2.12–16.92), and in animals kept in contact with sheep or goats (OR = 7.48, 95%CI: 2.56–21.86). Consequently, the camels may be a significant source of BVD infection for other ruminant animals in the same herd due to their susceptibility to the viral infection.

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.

Mitochondria-mediated ferroptosis contributes to the inflammatory responses of bovine viral diarrhea virus (BVDV) in vitro.

Bovine viral diarrhea virus (BVDV) belongs to the family Flaviviridae and includes two biotypes in cell culture: cytopathic (CP) or non-cytopathic (NCP) effects. Ferroptosis is a non-apoptotic form of programmed cell death that contributes to inflammatory diseases. However, whether BVDV induces ferroptosis and the role of ferroptosis in viral infection remain unclear. Here, we provide evidence that both CP and NCP BVDV can induce ferroptosis in Madin-Darby bovine kidney cells at similar rate. Mechanistically, biotypes of BVDV infection downregulate cytoplasmic and mitochondrial GPX4 via Nrf2-GPX4 pathway, thereby resulting in lethal lipid peroxidation and promoting ferroptosis. In parallel, BVDV can degrade ferritin heavy chain and mitochondrial ferritin via NCOA4-mediated ferritinophagy to promote the accumulation of Fe2+ and initiate ferroptosis. Importantly, CP BVDV-induced ferroptosis is tightly associated with serious damage of mitochondria and hyperactivation of inflammatory responses. In contrast, mild or unapparent damage of mitochondria and slight inflammatory responses were detected in NCP BVDV-infected cells. More importantly, different mitophagy pathways in response to mitochondria damage by both biotypes of BVDV are involved in inflammatory responses. Overall, this study is the first to show that mitochondria may play key roles in mediating ferroptosis and inflammatory responses induced by biotypes of BVDV in vitro.IMPORTANCEBovine viral diarrhea virus (BVDV) threatens a wide range of domestic and wild cattle population worldwide. BVDV causes great economic loss in cattle industry through its immunosuppression and persistent infection. Despite extensive research, the mechanism underlying the pathogenesis of BVDV remains elusive. Our data provide the first direct evidence that mitochondria-mediated ferroptosis and mitophagy are involved in inflammatory responses in both biotypes of BVDV-infected cells. Importantly, we demonstrate that the different degrees of injury of mitochondria and inflammatory responses may attribute to different mitophagy pathways induced by biotypes of BVDV. Overall, our findings uncover the interaction between BVDV infection and mitochondria-mediated ferroptosis, which shed novel light on the physiological impacts of ferroptosis on the pathogenesis of BVDV infection, and provide a promising therapeutic strategy to treat this important infectious disease with a worldwide distribution.

The impact of bovine viral diarrhoea virus on fertility in cattle and the protective effect of vaccination

Bovine viral diarrhoea virus (BVDV) infection is associated with significant reproductive losses in cattle through the detrimental impact of both persistent and transient infection on breeding females and males. The pathology within the reproductive tract is well described, although the mechanisms that lead to reproductive failure have yet to be fully unravelled. Prolonged shedding of virus following acute infection of bulls in both the peri- and post-pubertal periods has been observed, although the significance of this in relation to reproductive failure and the spread of infection has yet to be fully explored for the UK situation. Infection and recovery lead to an immune state in the female that is protective against breeding failure and generation of persistently infected calves. Vaccination using either of the two vaccines licensed for the control of BVDV infection in breeding cattle in the UK has been shown to be protective against fetal infection. In the UK where regional and herd level eradication of BVDV is progressing against a background of endemic infection, vaccination would appear to offer stopgap mitigation against reinfection until such times as national eradication is achieved.

Problems of cattle health improvement and protection of population against viral diarrhoea under current conditions of animal husbandry

The article presents the dynamics of the prevalence of bovine viral diarrhoea virus (BVDV) in livestock enterprises of the Ural region in the period 2018-2023. Retrospective and operational analysis of monitoring data showed that the epizootic situation was consistently tense. The share of unfavourable livestock enterprises ranged from 18.2% to 33.3%. The cumulative infection rate in different age groups of cattle ranged from 2.3% to 23.3%. Clinical symptoms of acute course of BVDV-infection in examined cattle were registered in 10.9% of cases; persistent form of BVDV-infection - in 16.5% of cases; subclinical course of BVDV-infection and latent form - in 73.6% of cases. Phylogenetic analysis of BVDV isolates obtained from animal biosamples showed that 81.8% of isolates belong to the Cp-biotype of BVDV, 18.2% of isolates - to the Ncpbiotype of BVDV. It has been established that the intensity of pathogen eradication decreases in livestock enterprises when the regulations of specific prophylaxis are violated, as evidenced by the increase in the number of animals carrying BVDV by 4%; calves with diseases caused by BVDV infection - by 2.5%; cows and heifers with reproductive losses - by 5.7%.

Comparative molecular detection of BVDV in cattle herds related to districts and seasons of year in Thi-qar province

Bovine viral diarrhea virus (BVDV) is a complicated ruminant pathogen that naturally infects cattle, goats, sheep, buffalo, pigs, camelids, and wild ruminants. BVDV infection causes serious financial losses, either directly due to high rates of mortality and morbidity brought on by fatal mucosal disease and immunosuppression. From September 2022 to May 2023, blood samples (225) were randomly collected from unvaccinated cattle from various regions within Thi-Qar province, Iraq. 5?-untranslated region (UTR) amplification by nested RT-PCR results showed that the distribution of bovine viral diarrhea virus in Thi-Qar province was 19.11% (43 out of 225). These results show no statistically significant differences in the bovine viral diarrhea virus distribution between geographical regions and study months (P &gt;0.05).

Unveiling tetrahydroquinolines as promising BVDV entry inhibitors: Targeting the envelope protein

Bovine viral diarrhea virus (BVDV) is known to cause financial losses and decreased productivity in the cattle industry worldwide. Currently, there are no available antiviral treatments for effectively controlling BVDV infections in laboratories or farms. The BVDV envelope protein (E2) mediates receptor recognition on the cell surface and is required for fusion of virus and cell membranes after the endocytic uptake of the virus during the entry process. Therefore, E2 is an attractive target for the development of antiviral strategies. To identify BVDV antivirals targeting E2 function, we defined a binding site in silico located in domain IIIc at the interface between monomers in the disulfide linked dimer of E2. Employing a de novo design methodology to identify compounds with the potential to inhibit the E2 function, compound 9 emerged as a promising candidate with remarkable antiviral activity and minimal toxicity. In line with targeting of E2 function, compound 9 was found to block the virus entry into host cells. Furthermore, we demonstrated that compound 9 selectively binds to recombinant E2 in vitro. Molecular dynamics simulations (MD) allowed describing a possible interaction pattern between compound 9 and E2 and indicated that the S enantiomer of compound 9 may be responsible for the antiviral activity. Future research endeavors will focus on synthesizing enantiomerically pure compounds to further support these findings. These results highlight the usefulness of de novo design strategies to identify a novel class of BVDV inhibitors that block E2 function inhibiting virus entry into the host cell.

The activation of liver X receptors in Madin-Darby bovine kidney cells and mice restricts infection by bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and is an important pathogen that represents a serious threat to the development of the cattle industry by causing significant economic losses. Liver X receptors (LXRs) are members of the nuclear receptor superfamily and have become attractive therapeutic targets for cardiovascular disease. In the present study, we found that LXRs in both Madin-Darby bovine kidney (MDBK) cells and mice were associated with BVDV infection. GW3965, an agonist for LXRs, significantly inhibited BVDV RNA and protein levels in MDBK cells. In vivo studies in a mouse model also confirmed the inhibitory role of GW3965 in BVDV replication and the ameliorating effect of GW3965 on pathological injury to the duodenum. In vitro investigations of the potential mechanisms involved showed that GW3965 significantly inhibited BVDV-induced increases in cholesterol levels and viral internalization. Furthermore, the antiviral activity of GW3965 was significantly reduced following cholesterol replenishment, thus demonstrating that cholesterol was involved in the resistance of GW3965 to BVDV replication. Further studies indicated the role of ATP-binding cassette transporter A1 (ABCA1) and cholesterol-25-hydroxylase (CH25H) in the antiviral activity of GW3965. We also demonstrated the significant antiviral effect of 25hydroxycholesterol (25HC), a product of the catalysis of cholesterol by CH25H. In addition, the anti-BVDV effects of demethoxycurcumin (DMC), cyanidin-3-O-glucoside (C3G), and saikosaponin-A (SSA), three natural agonizts of LXRs, were also confirmed in both MDBK cells and mice. However, the antiviral activities of these agents were weakened by SR9243, a synthetic inhibitor of LXRs. For the first time, our research demonstrated that the activation of LXRs can exert significant anti-BVDV effects in MDBK cells and mice.

Enhanced infectivity of bovine viral diarrhoea virus (BVDV) in arginase-producing bovine monocyte-derived macrophages

ABSTRACT Macrophages are important cells of the innate immunity that play a major role in Bovine Viral Diarrhea Virus (BVDV) pathogenesis. Macrophages are not a homogenous population; they exist in different phenotypes, typically divided into two main categories: classically (pro-inflammatory) and alternatively activated (anti-inflammatory) or M1 and M2, respectively. The role of bovine macrophage phenotypes on BVDV infection is still unclear. This study characterized the interaction between BVDV, and monocyte-derived macrophages (Mo-Mφ) collected from healthy cattle and polarized to an M1 or M2 state by using LPS, INF-γ, IL-4 or azithromycin. Arginase activity quantitation was utilized as a marker of the M2 Mo-Mφ spectrum. There was a significant association between arginase activity and the replication rate of BVDV strains of different genotypes and biotypes. Inhibition of arginase activity also reduced BVDV infectivity. Calves treated with azithromycin induced Mo-Mφ of the M2 state produced high levels of arginase. Interestingly, azithromycin administered in vivo increased the susceptibility of macrophages to BVDV infection ex vivo. Mo-Mφ from pregnant dams and calves produced higher arginase levels than those from non-pregnant adult animals. The increased infection of arginase-producing alternatively activated bovine macrophages with BVDV supports the need to delve into a possible leading role of M2 macrophages in establishing the immune-suppressive state during BVDV convalescence.

Development and evaluation of a monoclonal antibody-based blocking ELISA to detect antibodies against the E2 protein of bovine viral diarrhea virus-1

With the rapid development of cattle industry, bovine viral diarrhea virus (BVDV) is becoming widespread in China, which causes serious economic losses to the industry. Effective vaccination and viral surveillance are critical for the prevent and control of BVDV infection. In the present study, the immunogenic domain of E2 protein of BVDV-1 was expressed by prokaryotic pET-28a vector. Monoclonal antibodies (mAbs) against E2 protein were prepared and systemically examined by western blot, immunofluorescence assay, blocking ELISA (bELISA) and virus neutralization test (VNT). The mAb 1E2B3, which showed good reactivity and neutralizing activity to BVDV-1 strains, was selected for ELISA establishment. After a series of screening and optimization, a novel bELISA for highly sensitive and specific detection of BVDV-1 antibodies was established, using HRP-labeled 1E2B3 and recombinant E2 protein. ROC analysis of 91 positive and 84 negative reference bovine serum samples yielded the area under the curve (AUC) of 0.9903. A diagnostic specificity of 96.43 % and a sensitivity of 95.6 % were achieved when the cutoff value was set at 24.31 %. There was no cross reaction to the positive sera of classical swine fever virus (CSFV), BVDV-2, border disease virus (BDV), bovine parainfluenza virus type 3 (BPIV3), infectious bovine rhinotracheitis virus (IBRV), foot-and-mouth disease virus (FMDV), Mycoplasma bovis (M.bovis) and Brucella. The total agreement rate of bELISA with VNT was 93.96 % (249/265). In addition, the result of bELISA was positively correlated with neutralizing antibody titer, and the bELISA could well distinguish the serum samples before and after BVDV vaccination. These results indicate that the established bELISA in this study is specific, sensitive, simple and convenient, which provides technical support for the vaccine efficacy evaluation, prevention and control of BVD in the future.

Assessing the reliability of innovative criteria to certify that cattle are non-Persistently Infected (non-PI) with the Bovine Viral Diarrhoea Virus (BVDV)

Persistently Infected (PI) animals play a central role in the transmission of BVDV infection between cattle herds. Thus, promoting the certification of non-PI animals is a relevant approach for improving control, as it contributes to securing the trade. The objectives of this study were: i) to assess the reliability of diverse certification criteria, and ii) to identify risk factors for erroneous certification. To do so, the proportion of animals wrongly certified as non-PI on the basis of tests performed after the certification date, was calculated for each criterion. The data used were collected in herds located in Brittany, involved in either a clearance process for those that were infected, or in a surveillance process for herds that were BVDV-free. A total of 23 criteria were defined by combining the technical characteristics of the tests (individual vs. pool; single vs. repeated; direct vs. indirect tests), and some pathogenic characteristics of BVDV infection. Overall, the rates of wrongly-certified animals were low (mean: 1.3 10−4). Direct and indirect criteria had equivalent performances. Heifers from birth, and even foetuses in the last third of gestation, are certified, provided that the herd to which they belong has been free of BVDV for more than 2.5 years. The risk for wrong certification increased in the case of PIs present in the herd or its surroundings. The simplicity of the output-based approach described here, and the excellent performance of indirect criteria relying on serological monitoring of BTM, make it particularly interesting, as its use could facilitate trade between countries.

Integrative Transcriptomics and Proteomics Analysis Reveals Immune Response Process in Bovine Viral Diarrhea Virus-1-Infected Peripheral Blood Mononuclear Cells.

Bovine viral diarrhea virus (BVDV) causes bovine viral diarrhea-mucosal disease, inflicting substantial economic losses upon the global cattle industry. Peripheral blood mononuclear cells (PBMCs) are the central hub for immune responses during host-virus infection and have been recognized as crucial targets for BVDV infection. In order to elucidate the dynamics of host-BVDV-1 interaction, this study harnessed RNA-seq and iTRAQ methods to acquire an extensive dataset of transcriptomics and proteomics data from samples of BVDV-1-infected PBMCs at the 12-h post-infection mark. When compared to mock-infected PBMCs, we identified 344 differentially expressed genes (DEGs: a total of 234 genes with downregulated expression and 110 genes with upregulated expression) and 446 differentially expressed proteins (DEPs: a total of 224 proteins with downregulated expression and 222 proteins with upregulated expression). Selected DEGs and DEPs were validated through quantitative reverse transcriptase-polymerase chain reaction and parallel reaction monitoring. Gene ontology annotation and KEGG enrichment analysis underscored the significant enrichment of DEGs and DEPs in various immunity-related signaling pathways, including antigen processing and presentation, complement and coagulation cascades, cytokine-cytokine receptor interaction, and the NOD-like receptor signaling pathway, among others. Further analysis unveiled that those DEGs and DEPs with downregulated expression were predominantly associated with pathways such as complement and coagulation cascades, the interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, the PI3K-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the NOD-like receptor signaling pathway. Conversely, upregulated DEGs and DEPs were chiefly linked to metabolic pathways, oxidative phosphorylation, complement and coagulation cascades, and the RIG-I-like receptor signaling pathway. These altered genes and proteins shed light on the intense host-virus conflict within the immune realm. Our transcriptomics and proteomics data constitute a significant foundation for delving further into the interaction mechanism between BVDV and its host.

Bovine Viral Diarrhea Virus Antibody Level Variation in Newborn Calves after Vaccination of Late-Gestational Cows.

This study was conducted to confirm variation in bovine viral diarrhea virus (BVDV) antibody levels transferred to calves from their mother's colostrum after vaccination of late-gestational cows. Blood samples were drawn from 60 pregnant cows that had been vaccinated more than one year and less than two years previously. The samples were collected six weeks prior to the expected date of delivery. After sample collection, the cows were divided into two groups of 30. One group received 2 mL of BVDV vaccine, and a control group received 2 mL of phosphate-buffered saline (PBS). Blood was collected from the cows three weeks post-administration. Additional blood samples were taken from calves at 1, 4, 8, 12, 16, and 20 weeks after birth. The serum was separated from the collected blood, and BVDV antibody changes were confirmed by enzyme-linked immunosorbent assays. BVDV antibody levels were higher from 8 to 20 weeks of age in calves born to late-gestational BVDV-vaccinated cows than in calves born to control cows (p < 0.0083). Further analysis confirmed a slow decline in BVDV maternal antibodies in calves born to pregnant cows that produced high levels of BVDV antibodies following pre-calving BVDV vaccination. These results suggest that BVDV vaccination of cattle in late pregnancy may help to extend the duration of protection against BVDV infection in newborn calves.

Comparative Analysis of the Prevalence of Bovine Viral Diarrhea Virus in Cattle Populations Based on Detection Methods: A Systematic Review and Meta-Analysis.

Infectious diseases of cattle, including bovine viral diarrhea (BVD), pose a significant health threat to the global livestock industry. This study aimed to investigate the prevalence and risk factors associated with bovine viral diarrhea virus (BVDV) infections in cattle populations through a systematic review and meta-analysis. PubMed, Web of Science, and Scopus were systematically searched for relevant articles reporting the prevalence of and associated risk factors in studies published between 1 January 2000 and 3 February 2023. From a total of 5111 studies screened, 318 studies were included in the final analysis. BVDV prevalence in cattle populations was estimated using various detection methods. The analysis detected heterogeneity in prevalence, attributed to detection techniques and associated risk factors. Antibody detection methods exhibited a higher prevalence of 0.43, reflecting the cumulative effect of detecting both active and past infections. Antigen detection methods showed a prevalence of 0.05, which was lower than antibody methods. A prevalence of 0.08 was observed using nucleic acid detection methods. The health status of the examined cattle significantly influenced the prevalence of BVDV. Cattle with bovine respiratory disease complex (BRDC) exhibited higher antibody (prevalence of 0.67) and antigen (prevalence 0.23) levels compared to cattle with reproductive problems (prevalence 0.13) or diarrhea (prevalence 0.01). Nucleic acid detection methods demonstrated consistent rates across different health conditions. Age of cattle influenced prevalence, with higher rates in adults compared to calves. Risk factors related to breeding and reproduction, such as natural or extensive breeding and a history of abortion, were associated with increased prevalence. Coinfections with pathogens like bovine herpesvirus-1 or Neospora caninum were linked to higher BVDV prevalence. Management practices, such as commingling, introducing new cattle, and direct contact with neighboring farms, also influenced prevalence. Herd attributes, including larger herd size, and the presence of persistently infected cattle, were associated with higher prevalence. These findings indicated the importance of detection methods and risk factors in BVDV epidemiological studies.