Transmission Of Bovine Viral Diarrhea Virus Research Articles

Herd‐Level Modeling of Bovine Viral Diarrhea Virus (BVDV) Transmission in Cattle Herds in Southern Chile: Linking Within and Between‐Herd Dynamics

Bovine viral diarrhea (BVD) represents a serious threat to the cattle sector in Chile, indicating the need for a regionally defined control program. Ex-ante evaluations of program options using simulation modeling have proven to be a successful approach in providing decision‐makers with relevant supporting insights in that respect. Given the complexity of bovine viral diarrhea virus (BVDV) infection dynamics, simulation of BVD spread in a metapopulation requires detailed consideration of both within and between herd transmission dynamics. The aims of the study are (i) to investigate the dynamics of BVDV transmission in cattle herds in southern Chile by linking a within‐herd transmission model (WHM) that accounts for the BVDV’s unique characteristics with a between‐herd model (BHM) that meets the demands for further regional control strategy evaluation; (ii) to suggest and discuss criteria for evaluation of the model approach and plausibility for later research and for support decision‐making. This resulted in bringing forth a modeling rationale for complex disease spread simulation in metapopulations. BHM simulations under this approach show outcomes that agree with BVDV’s known situation in Chile; dairy herds prevalence at endemic equilibrium reaches and maintains 75%, which agrees with estimations of BVDV active infection in dairy herds in southern Chile (77%). For the entire herd population, the infection always reaches endemic levels with a large proportion of infected herds (median = 60%), where herd prevalence was higher in the dairy herd class than in the remaining categories. Transmission probability variation affects the new infections picked, prevalence at endemic levels, and the velocity in which the infection spreads between herds. The fact that the presented approach was able to model a complex infection dynamic such BVDV, with sufficient confidence, provides evidence that this approach can be used to explore mitigation strategies to control BVDV in southern Chilean herds.

Replication of standard bovine viral diarrhea strain OregonC24Va induces endoplasmic reticulum stress-mediated apoptosis of bovine trophoblast cells.

Bovine viral diarrhea (BVD) is a worldwide infectious disease caused by bovine viral diarrhea virus (BVDV) infection, which invades the placenta, causes abortion, produces immune tolerance and continuously infects calves, and causes huge economic losses to the cattle industry. The endoplasmic reticulum (ER) is an important organelle in cells, which is prone to ER stress after being stimulated by pathogens, thus activating the ER stress-related apoptosis. Studies have confirmed that BVDV can utilize the ER of its host to complete its own proliferation and stimulate ER stress to a certain extent. However, the role of ER stress in BVDV infecting bovine placental trophoblast cells (BTCs) and inducing apoptosis is still unclear. We are using the cytopathic strain of BVDV (OregonC24Va), which can cause apoptosis of BTCs, as a model system to determine how ER stress induced by BVDV affects placental toxicity. We show that OregonC24Va can infect BTCs and proliferate in it. With the proliferation of BVDV in BTCs, ER stress-related apoptosis is triggered. The ER stress inhibitor 4-PBA was used to inhibit the ER stress of BTCs, which not only inhibited the proliferation of BVDV, but also reduced the apoptosis of BTCs. The ER stress activator Tg can activate ER stress-related apoptosis, but the proliferation of BVDV does not change in BTCs. Therefore, BVDV utilizes the UPR of activated ER stress to promote the proliferation of BVDV in the early stage of infection, and activates the ER stress-related apoptosis of BTCs in the later stage with the virus proliferation to promote the cell apoptosis and further spread of the virus. Our research provides a new theoretical basis for exploring the placental infection and vertical transmission of BVDV.

Temporal and geographic dynamics of bovine viral diarrhea virus in American countries

Bovine viral diarrhea virus (BVDV) is a worldwide distributed pathogen of livestock classified into three species, BVDV-1 (Pestivirus A), BVDV-2 (Pestivirus B), and HoBi-like pestivirus (HoBiPeV; Pestivirus H). Despite being considered endemic in several regions of the Americas, the spatiotemporal distribution of BVDV is scarcely known. This study aimed to reconstruct the population dynamics of BVDV in American countries. The analyses performed with the partial 5´UTR gene showed that BVDV-1 and -2 would have started their diversification in the 1670s and 1790s in the United States, whereas HoBiPeV probably emerged in the 1980s in Brazil. No evident geographic clustering was observed in the Bayesian trees, which may indicate that multiple introductions events would have occurred following the first introduction. This study provides new insights into BVDV dynamics, although further analyses including sequences from other American countries and continents will help to expand the knowledge of BVDV evolution and transmission.

Risk-associated factors associated with the bovine viral diarrhea virus in dromedary camels, sheep, and goats in abattoir surveillance and semi-closed herd system.

Background and Aim:Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens causing high economic losses in cattle of all ages. Despite the active vaccination campaigns against BVDV, many outbreaks are still detected in various populations of cattle worldwide. Other species of animals such as dromedary camels, sheep, and goats may harbor BVDV infection and cause variable clinical syndromes. Thus, they may act as a source of infection to the cattle population around them. However, little is still known about the roles of these animals in the viral transmission and sustainability of BVDV in the environment. This study aimed to explore if the dromedary camels, sheep, and goats may seroconvert against BVDV and to study some associated risk factors for BVDV in these species of animals.Materials and Methods:We tested 1012 serum samples from dromedary camels, 84 from goats, and 21 from sheep for BVDV antibodies using commercial enzyme-linked immunosorbent assay (ELISA) kits. Meanwhile, we selected 211 serum samples from dromedary camels to be tested for the BVDV antigen using the commercial ELISA kits.Results:Our results show that 49/1117 serum samples were positive for the BVDV antibodies in dromedary camels (46/1012), goats (3/84), and none of the tested sheep samples were positive. However, none of the collected serum samples tested positive for the BVDV antigen.Conclusion:Seroconversion of some dromedary camels, sheep, and goats to the BVDV with no history of vaccination against BVDV strongly suggests the potential roles of these species of animals in the virus transmission cycle. The main limitations of the current study are (1) the lack of samples from other species of animals that lived close by these animals, particularly cattle. (2) lack of follow-up samples from the same animal over a long period. We believe the long-term longitudinal study of BVDV in various species of animals, particularly dromedary camels, goats, and sheep, is one of our future research directions. This will provide more information about the dynamics of BVDV antibodies in these species of animals.

The Epidemiology and Control of Bovine Viral Diarrhoea Virus in Tropical Indonesian Cattle.

This review aims to update the knowledge of the epidemiology of Bovine viral diarrhoea virus (BVDV) in Indonesia and Southeast Asia and provide a perspective on the control options for BVDV in the Indonesian cattle population in the future. Studies on BVDV in Indonesia, since its first report in that country, and the updated beef and dairy cattle industries are reviewed. In ten of 34 provinces, BVDV is endemic. The subgenotypes of BVDV-1a and BVDV-1c are predominant in Indonesian cattle. However, BVDV is currently not a priority disease to control in Indonesia. Cattle imports from Australia appear to be potentially the most significant source of transmission of BVDV into native cattle, but the control of BVDV conducted in the local quarantine facilities is currently not achieving the aim of controlling BVDV; thus, complementary measures are needed. With the small-scale nature of the vast majority of cattle breeding in the country, the control of BVDV in provinces in which cattle breeding is economically essential may need to be organised by regional and provincial governments. Gaps in our knowledge of BVDV are identified in this review, and strategies for the control of BVDV in Indonesia are discussed.

Modeling the Effect of Bovine Viral Diarrhea Virus in Australian Beef Herds.

Bovine viral diarrhea virus (BVDV) is an economically important disease in Australian beef farming. The disease typically results in low-level production losses that can be difficult to detect for several years. Simulation modeling can be used to support the decision to control BVDV; however, current BVDV simulation models do not adequately reflect the extensive farming environment of Australian beef production. Therefore, the objective of this study was to develop a disease simulation model to explore the impact of BVDV on beef cattle production in south-east Australia. A dynamic, individual-based, stochastic, discrete-time simulation model was created to simulate within-herd transmission of BVDV in a seasonal, self-replacing beef herd. We used the model to simulate the effect of herd size and BVDV introduction time on disease transmission and assessed the short- and long-term impact of BVDV on production outputs that influence the economic performance of beef farms. We found that BVDV can become established in a herd after a single PI introduction in 60% of cases, most frequently associated with the breeding period. The initial impact of BVDV will be more severe in smaller herds, although self-elimination is more likely in small herds than in larger herds, in which there is a 23% chance that the virus can persist for >15 years following a single incursion in a herd with 800 breeders. The number and weight of steers sold was reduced in the presence of BVDV and the results demonstrated that repeat incursions exacerbate long-term production losses, even when annual losses appear marginal. This model reflects the short- and long-term production losses attributed to BVDV in beef herds in southeast Australia and provides a foundation from which the influence and economic utility of BVDV prevention in Australian beef herds can be assessed.

Non-Bovine Species and the Risk to Effective Control of Bovine Viral Diarrhoea (BVD) in Cattle.

Bovine viral diarrhoea virus (BVDV) is an economically important and highly prevalent virus of domestic cattle. Infections with BVDV may lead to both, reproductive and immunological effects that can result in widespread calf losses and increased susceptibility to diseases, such as mastitis and respiratory disease. While BVDV is generally considered to be host specific, it and other Pestivirus species, such as Border disease virus (BDV) in sheep, have been shown to be infecting species other than those from which they were originally isolated from. Recently BVDV was placed on the OIE’s list of notifiable disease and control and eradication programmes for BVDV have been developed throughout much of Europe, the United States, and the United Kingdom. While some countries, including Sweden and Ireland have successfully implemented eradication programmes, other countries such as New Zealand and Australia are still in the early stages of BVDV control. Despite effective control methods, incursions of BVDV into previously cleared herds still occur. While the cause of these incursions is often due to lapses in control methods, the ability of ruminant pestiviruses to infect species other than cattle poses the question as to whether non-bovine species could be impeding the success of BVDV eradication and control. As such, the aim of this review is to make mention of what is known about the cross-species transmission of BVDV, BDV and other pestiviruses between cattle and non-bovine ungulate species and draw conclusions as to the risk non-bovine species pose to the successful control and eradication of BVDV from cattle.

Clinical Analysis for Long-Term Sporadic Bovine Viral Diarrhea Transmitted by Calves with an Acute Infection of Bovine Viral Diarrhea Virus 2

Bovine viral diarrhea virus (BVDV) is a viral pathogen associated with serious problems in the cattle industry. Cattle persistently infected (PI) with BVDV are mild or asymptomatic; however, they become a source of BVDV transmission to other cattle. Hence, it is important to rapidly identify and remove the PI animals from cattle herds. Whereas cattle acutely infected (AI) with BVDV have various symptoms, yet they generally recover within 3 weeks. However, there is a paucity of information concerning clinical characteristics of AI cattle. Further accumulation of information would be required to accurately diagnose AI cattle with BVDV. Here, we attempted to obtain valuable information via various analyses using a case report of BVD outbreak that occurred for approximately four months in Iwate Prefecture in 2017. Using eight calves and multiple tests (real-time RT-PCR, virus isolation, enzyme-linked immunosorbent assay, and virus neutralization assay) over 6 weeks, we diagnosed the continuous BVD outbreak as an acute infection and not a persistent one. Additionally, we revealed that the sporadic case was caused by low pathogenic BVDV2 via BVDV genotyping and phylogenetic analysis. The data suggest that BVDV2 AI animals might also be a source of transmission to susceptible calves; hence, it might persist for a long period owing to multiple AI animals. These findings provide useful information to diagnose AI and PI cattle with BVDV in the field.

Temporal trends in bulk tank milk antibody ELISA and PCR test results for bovine viral diarrhoea in New Zealand pastoral dairy herds

ABSTRACT Aims: To describe temporal trends in bulk milk antibody ELISA and PCR testing for bovine viral diarrhoea (BVD) in New Zealand pastoral dairy herds and to assess the use of historical accession data to predict herd-level BVD incursions. Methods: Data on all diagnostic testing of bulk milk for BVD performed by the Livestock Improvement Corporation (Hamilton, NZ) over eight lactation seasons from 1 June 2010 to 31 May 2018 were analysed. This included anonymised herd identification, geographic location, herd size, sample collection date, sample to positive (S/P) ratio for antibody ELISA results, and cycle threshold values for PCR detecting viral RNA. Multivariable logistic regression was used to explore the relationship between historical accession data and the risk of herds having at least one positive bulk milk PCR test result in the 2017 season. Results: There were 156,034 bulk milk BVD diagnostic testing accessions for 10,495 uniquely identified dairy herds over the 8-season period. The prevalence of tested herds with at least one positive bulk milk PCR test result decreased from 14.6% (407/2,786) in the 2010 season to 5.6% (355/6,309) in the 2017 season with similarly marked declines in S/P ratios. In the 2017 season, 2,961/6,309 (46.9%) herds had S/P ratios greater than the 0.75 cut-off value indicating recent or active BVD virus transmission within the herd while 1,422/6,309 (22.5%) herds were classified as having negative or low S/P ratios. Herds that cleared BVD from the milking herd experienced a mean decline in S/P ratio of 0.11 units per year (min 0.05; max 0.18). In the multivariable analysis, the overall incidence risk of herds experiencing a BVD incursion in the 2017 season was 3.8% (146/3,848) and there were three significant predictors in the final model: herd size, PCR status in the 2014 season, and change in S/P ratio between the 2014 and 2015 seasons. The area under the receiver operating curve for the final model was 0.695 indicating poor discrimination. Conclusions and clinical relevance: The prevalence of dairy herds in New Zealand with positive bulk milk PCR test results and high S/P ratios has decreased over time, suggesting fewer herds are actively infected with BVD and that herd immunity may also be declining. Although monitoring trends in bulk milk test results provides useful information on changes in individual herd status, it is difficult to accurately predict when new incursions will occur and farmers should continue to maintain good biosecurity.

A description and qualitative comparison of the elements of heterogeneous bovine viral diarrhea control programs that influence confidence of freedom

For endemic infections in cattle that are not regulated at the European Union level, such as bovine viral diarrhea virus (BVDV), European Member States have implemented control or eradication programs (CEP) tailored to their specific situations. Different methods are used to assign infection-free status in CEP; therefore, the confidence of freedom associated with the "free" status generated by different CEP are difficult to compare, creating problems for the safe trade of cattle between territories. Safe trade would be facilitated with an output-based framework that enables a transparent and standardized comparison of confidence of freedom for CEP across herds, regions, or countries. The current paper represents the first step toward development of such a framework by seeking to describe and qualitatively compare elements of CEP that contribute to confidence of freedom. For this work, BVDV was used as a case study. We qualitatively compared heterogeneous BVDV CEP in 6 European countries: Germany, France, Ireland, the Netherlands, Sweden, and Scotland. Information about BVDV CEP that were in place in 2017 and factors influencing the risk of introduction and transmission of BVDV (the context) were collected using an existing tool, with modifications to collect information about aspects of control and context. For the 6 participating countries, we ranked all individual elements of the CEP and their contexts that could influence the probability that cattle from a herd categorized as BVDV-free are truly free from infection. Many differences in the context and design of BVDV CEP were found. As examples, CEP were either mandatory or voluntary, resulting in variation in risks from neighboring herds, and risk factors such as cattle density and the number of imported cattle varied greatly between territories. Differences were also found in both testing protocols and definitions of freedom from disease. The observed heterogeneity in both the context and CEP design will create difficulties when comparing different CEP in terms of confidence of freedom from infection. These results highlight the need for a standardized practical methodology to objectively and quantitatively determine confidence of freedom resulting from different CEP around the world.

Evidence of bovine viral diarrhea virus transmission by back pond water in experimentally infected piglets

ABSTRACT: Swine can be infected by bovine viral diarrhea virus (BVDV). However, transmission routes among pigs are still unknown. The objective of the present study was to induce experimental infection of BVDV-1 in weaned piglets and to assess the potential transmission through pen back pond water, used to facilitate heat exchange of the pigs housed in barns. Two repetitions (BP1 and BP 2) were performed using 12 piglets proven to be free BVDV (n=6 per repetition) allocated into three groups: control, sentinels and infected with two piglets each. The piglets were placed in stainless steel isolators. The infected group received an inoculum containing BVDV-1, Singer strain. The piglets remained in the cabinets for 25 days, during which samples of nasal swab were collected daily and blood sampled weekly. At the end, the piglets were euthanized, necropsied and organ fragments were collected for histopathology, immunohistochemistry and RT-PCR. In the first experiment (BP1) the infected animals shed the virus between days 6 and 21 post-infection. Regarding the sentinel group, shedding occurred in only one piglet, on the 20th day after infection, and seroconversion was observed on the 25th day post-infection. In BP2, infected piglets I3 and I4 shed the virus on days 4 and 21 post-infection, respectively. Only one sentinel piglet (S3) she the virus on day 13 post-infection. Therefore, it was concluded that pigs can become infected with BVDV-1 and shed potentially infectious viral particles consequently, being able to transmit the virus to other pigs through back pond water.

Detecção do vírus da diarreia viral bovina em carrapatos Rhipicephalus (Boophilus) microplus alimentados e, bovino persistentemente infectado

Background: Bovine viral diarrhea virus (BVDV) is one of the main agents that cause economical losses in cattle worldwide. Congenitally infected calves that are born persistently infected (PI) to BVDV are the main sources of infection to susceptible cattle. Direct contact is the most important form of transmission, but indirect contact can also spread BVDV, not only inside herds, but also between them. Transmission of BVDV by haematophagous insects has been proven experimentally, but the role of ticks in the transmission of BVDV has never been investigated. Ticks can heavily infest cattle raised in tropical areas and Rhipicephalus (Boophilus) microplus is the most important among them. The present experiment was carried out to investigate the role of R. microplus ticks in the transmission of BVDV, experimentally infecting PI calf with ticks. Material, Methods and Results: Three calves were used in the experiment: one PI calf was identified from a natural outbreak; a second animal was infested with the progeny of a tick fed on the PI calf and the third was kept as a negative control, infested with negative ticks. Viral RNA investigation was performed by reverse transcription followed by polymerase chain reaction (RT-PCR) from the sera of the calves and from ticks (adult females, eggs and larvae that were the progeny of the experimentally contaminated adult females and from the control animal). BVDV RNA was detected in tick adult females fed on the PI calf, but not in the control animal. Experimental infestation of a second cattle with larvae derived from adult females infected with BVDV was not able to produce infection. These data suggest that the virus is able to pass to ticks during feeding on the infected PI animal, but that there is no transmission by transovarial route, as viral RNA was not detected in eggs and larvae from adult females infected with BVDV. Discussion: Bovine tick is the most important ectoparasite in domestic animals in tropical and subtropical areas. However, its role in transmission of viral agents, particularly BVDV, has not been previously studied. The results of our experiment suggested that adult females of R. microplus were not able to transmit the infection to susceptible cattle. However, a macerate of a pool of tick females fed on the PI calf was positive to BVDV. A further validation using a larger number of infested bovines would help to confirm this new finding. R. microplus ticks are monoxenic, but it must be considered that the males, different from females, make a non-continual process of blood sucking and may move between bovines to reproduce. Additionally, in conditions of close contact between animals, besides tick males, larvae may change hosts in the early stages of development. These facts do not permit to exclude the risk of direct spread of viral infection in the herd by a same specimen of R. microplus. On the other hand, the presence of virus inside females represents an environmental reservoir of BVDV, which may infect through epithelial abrasions if ingested. These considerations may be reinforced by the fact that in field conditions it has been observed that high animal density favors the fast spread of BVDV in cattle herds. Collectively, these evidences suggest that ticks would represent an additional factor to be allowed for in BVDV transmission. As a conclusion, the present study demonstrates that R. microplus can be contaminated with BVDV during blood feeding, strengthening the idea that haematophagous vectors can be involved in the spread of the disease. In spite of the fact that BVDV was not transmited by the progeny of the ticks, it is not possible to discard such form of transmission under natural conditions.

Evaluation of bovine viral diarrhea virus transmission potential to naïve calves by direct and indirect exposure routes

Bovine viral diarrhea viruses (BVDV) can cause both acute and persistent infections in cattle. Exposure to BVDV persistently infected (PI) animals results in transmission of the virus to a naïve animal which causes a transient acute infection. While it is known that direct exposure to PI animals is a highly efficient means of transmission, less information is available regarding the potential for transmission from acutely infected either by direct or indirect exposure to naïve animals. Therefore, the objective of this study was to evaluate the potential for spread of the virus from calves acutely infected, with typical virulence field viruses know to have minimal shedding and viremia, to naïve contact animals either by direct or indirect exposure. To accomplish this objective, two BVDV isolates belonging to two species of BVDV, type 1 and type 2, were used to inoculate calves. Subsequently on day 2 post-infection, naïve calves were exposed to inoculated calves, either directly or indirectly, over a period of two weeks. All calves were evaluated for the presence of virus in blood samples and nasal swabs, pyrexia, lymphopenia and seroconversion. BVDV was isolated from inoculated calves but not from any of the direct and indirect contact animals or from control calves. Similarly, pyrexia and lymphopenia were observed in the inoculated calves, but not in contact and control calves. Only the inoculated calves seroconverted by day 38 of the study indicating that no transmission had occurred to the naïve contact calves. This data would suggest that there may be an infectious dose needed for transmission of virus for typical virulent isolates.

Identification of Bovine Viral Diarrhoea Virus Type 2 in Cattle Bull Semen from Southern India and its Genetic Characterization

Although bovine viral diarrhoea virus (BVDV) is prevalent in Indian cattle causing economic losses in cattle farming, its detection in bull semen has not yet been reported. Following passage of raw bull semen (n = 4) on MDBK cells, testing for BVDV was done by antigen ELISA and real-time RT-PCR. BVDV type-2 (BVDV-2) was identified in three samples from southern India by real-time RT-PCR. Genetic typing of the 5'-UTR sequences classified all the three BVDV strains as BVDV-2a subtype. These were found genetically closely related to the strains from USA, but divergent from the BVDV-2a strains from northern India. Phylogenetic analysis of N pro sequences confirmed the findings. The results provide evidence of circulation of BVDV-2a strains in southern India. The detection of BVDV in bull semen from India highlights the importance of mandatory testing of breeding bulls and bull semen for BVDV to minimize the risk of BVDV transmission.

The risk of transmission from sheep experimentally infected with BVDV-1c during the acute phase to BVDV naïve sheep

Bovine viral diarrhoea virus (BVDV) is an economically important disease of cattle known to cause immunosuppression and reproductive dysfunction in infected animals. Although predominantly a disease of cattle other ruminant species, such as sheep, have been shown to undergo infection with similar outcomes as those observed in cattle.The main source of BVDV transmission is known to be persistently infected (PI) animals which shed large quantities of virus through all secretions and excretions. However, it is believed that BVDV is able to persist within herds even after the removal of these PI animals. Although not proven, this persistence is thought to be due to the short period of viral excretion shown to occur in acutely infected animals. As a result the aim of this study was to determine if transmission of BVDV could occur between sheep undergoing an acute BVDV infection and sheep naïve to BVDV.Five wethers, experimentally infected with BVDV-1c, were co-mingled with five pestivirus naïve wethers for a period of seven weeks. Weekly blood samples were collected and tested for the presence of BVDV-specific antibodies and BVDV antigen. Acute infection was successful in the experimentally inoculated animals, with antibodies detected in all five wethers by Day 35 post inoculation. Transmission of BVDV-1c was not shown to occur between these acutely BVDV-1c infected wethers and the naïve wethers co-mingled with them.

Co-infection with bovine viral diarrhoea virus and Anaplasma marginale in a dairy cattle herd may lead to acute bovine anaplasmosis

This report describes an acute exacerbation of subclinical anaplasmosis manifesting itself in clinical signs in a large number of animals after infection with bovine viral diarrhoea virus (BVDV). The simultaneous transmission of BVDV and Anaplasma was unintended and most likely the result of a vaccination operation in a large Holstein-Friesian dairy cattle herd in Hungary. From Day 35 after the first vaccination, a total of 33 cows developed fever, depression, general weakness, lack of appetite, a sudden drop of milk production, anaemia, icterus, and tachypnoea on exercise. In addition, a total of seven abortions and three stillbirths occurred. Between Days 30 and 35 after the second vaccination four cows showed clinical signs typical of anaplasmosis, and two stillbirths occurred. The presence of Anaplasma marginale infection was demonstrated by haematological, biochemical, PCR and haemocytological examinations of blood samples collected from animals showing clinical signs as well as by necropsy. To assess the prevalence of infection in the herd, a specified number of animals belonging to different age groups were subjected to serological tests. The rate of seropositive animals was substantially higher (50%) in the older (3- to 4-year-old and more than 4-year-old) age groups than in the younger cows (10–30%). This study has demonstrated for the first time that if bovine animals susceptible to both A. marginale and BVDV are infected by the two pathogens roughly at the same time, the immunosuppressive effect of BVDV will support the progression of A. marginale infection and manifestation of the disease resulting in acute clinical signs.

Soluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the bovine pestivirus.

The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides, 66EQIV69 and 82GQVLAL87, located on antiparallel beta sheets in the most distal complement control protein module (CCP1), provide the attachment platform. In the present study, we reveal new CD46-encoding transcripts that are predicted to encode CCP1-containing soluble forms. Further, we show that the serum of most adult cattle contains soluble CD46 (sCD46) and that a recombinant soluble isoform neutralizes BVDV infectivity in an in vitro assay. We have then established an ELISA for determination of plasma sCD46 in a large cohort of animals. Overall, serum sCD46 amounts to 8±18ng/mL (mean±SD, n=440), with a IC [95-105] ranging from 6,4 to 9,8ng/mL and extreme values ​​between 0 and 178ng/mL. We found that sCD46 is not detectable in fetal and neonatal sera and that its plasma concentration increases progressively up to adulthood. We also detected high- and low-sCD46 performers and show that this phenotype does not depend of environment. As modern rearing techniques make it possible to disseminate genetically-determined phenotypes very quickly in a population, a large-scale study examining whether high-sCD46 animals provide epidemiological protection against BVDV infection and transmission should be undertaken.

Bovine Leukosis Virus and Antibodies against Bovine Herpesvirus Type-1 and Bovine Viral Diarrhea Virus and in Buffaloes of the State of Pará, Brazil

Background: Viral diseases affecting reproduction cause economic losses in cattle, as reproductive failure interrupts the production cycle, thus reducing herd productivity. Buffaloes are susceptible to most of the diseases that affect cattle. Some of the viral diseases of reproductive importance are infectious bovine rhinotracheitis (IBR), bovine viral diarrhea (BVD), and bovine leukosis (BL). The objective of this study was to determine the seroprevalence of IBR virus (bovine herpes virus-1, BoHV-1), BVD virus (BVDV), and BL virus (BLV) in female buffaloes living in wetland areas or plains in the state of Pará, as well as the seroprevalence of BoHV-1, BVDV, and BLV in females of different age groups.Materials, Methods & Results: It were used 225 crossbred buffaloes from 4 buffalo exclusive farms. The buffaloes reared on farms A (n = 50) and B (n = 89) were kept in wetland areas on Marajó Island (n = 139), Pará. On farms C (n = 30) and D (n = 56) buffaloes were kept in plains (n = 86) in a northeastern mesoregion of Para. Animals were categorized into age groups: I: 0-3 years (n = 34), II: 3-6 years (n = 58), III: 7-9 years (n = 55), and IV: over 9 years (n = 78). Blood samples were collected and sera were sent for processing at the Bovine Virus Laboratory, Biological Institute of São Paulo, Brazil. The presence of IBRV and BVDV was determined by neutralization and BLV antibodies by immunodiffusion in agar gel. Statistical analysis was performed using the Ȥ2 test at a significance level of 5%. Among the seroprevalences of IBRV, BVDV and BLV antibodies, the difference in prevalence for BVD [P < 0.01] was observed between wetland areas and plains of Para, varying from 12.4% to 96.0% and 0.0% to 13.3%, respectively. While levels of IBRV remained high on farms A (79.6%), B (86.5%), C (83.3%) and D (89.1%) [P = 0.60] and BLV was negative in all the animals. BVDV was similar for all the age groups [P = 0.60], while IBRV was more prevalent in animals over 6 years of age with group I: (76.5%), II (74.5%), III (92.3%) and IV (91.3%) [P = 0.01]. It was not possible verify the influence of age in prevalence for BL.Discussion: The prevalence obtained for the BoHV-1 on farms was high, with little variation between 79.6% and 89.1%. The high prevalence of BoHV-1 suggests the free circulation of the virus in the state of Para. Notably, the animals in this study had not been vaccinated, so the determined viral antibody titers were independent of vaccination. BVDV results showed high variation between 0.0% and 96.0%. The highest prevalence in wetland areas may be related to the breeding environment, because of a possible horizontal contamination. The lack of BLV antibodies prevalence can be attributed to the fact that all the evaluated animals were kept in an extensive breeding system where they had little direct contact. The prevalence of IBR was higher in the older animals. Variation in prevalence with age was not observed for BVD. It was concluded that the prevalence for IBR and BVD were high indicating that the etiological agents are circulating in Para, with IBR having a higher prevalence in older animals. Breeding buffalo in wetland areas may favor horizontal transmission of BVDV because facilitate contact of healthy animals with water contaminated by virus carriers animal secretion and the absence of seropositive animals at the BLV does not necessarily indicate that buffaloes are resistant to the virus.

Persistent Bovine Viral Diarrhea Virus Infection in Domestic and Wild Small Ruminants and Camelids Including the Mountain Goat (Oreamnos americanus).

Bovine viral diarrhea virus (BVDV) is a pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus).

Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle.

Bovine viral diarrhea virus (BVDV), a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI) cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution.