BVDV GENOMIC ORGANIZATION AND PROTEINS. Eugene Berry Department of Veterinary & Microbiological Sciences, North Dakota State University

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1 BVDV GENOMIC ORGANIZATION AND PROTEINS Eugene Berry Department of Veterinary & Microbiological Sciences, North Dakota State University BVDV, currently classified in the pestivirus genus of the family Flaviviridae, are small, enveloped viruses having a single-stranded positive-sense RNA genome. The BVDV genome is approximately 12.3 kb in length with a 5'-nontranslated region (NTR), a single large open reading frame (ORF), and a 3'-NTR lacking a poly(a)tail. The 5'-NTR contains an internal ribosome entry site that initiates translation of BVDV mrna in a cap-independent manner. The secondary structure of the 5'-NTR is involved in the regulation of both translation and genome replication. The ORF is translated into a single polyprotein of approximately 4000 amino acids that is co- and post-translationally cleaved into 11 or 12 mature proteins by viral and host proteases. The order of proteins in the polyprotein is Npro (a nonstructural autoprotease unique to pestiviruses), the capsid protein (C), the envelope glycoproteins (Erns, E1, and E2), and the nonstructural proteins (p7, NS2/NS3, NS4A, NS4B, NS5A, and NS5B). NS3 (NS2/NS3) has helicase, serine protease, and NTPase activities, and NS5A has RNA-dependent RNA-polymerase activity. The NS2/NS3 complex is not cleaved in BVDV isolates that are noncytopathic in cell culture, while in isolates that are cytopathic both NS2/NS3 and a discrete NS3 are observed. The processing of NS2/NS3 appears to develop from RNA recombination events during the genomic replication of a noncytopathic virus. As a result, the genome of cytopathic isolates may contain genomic duplications, deletions, rearrangements, and/or insertions of cellular mrna.

2 BVDV BIOTYPES AND GENOTYPES Julia Ridpath NADC/ARS/USDA BVDV is an umbrella term for a diverse group of viruses from the pestivirus genus. There are two genotypes of BVDV, BVDV1 and BVDV2. Recently, these two genotypes have been declared separate and distinct species. Frequently differentiation between BVDV1 and BVDV2 is made based on comparison of sequences from the 5' untranslated region (5' UTR). This region is highly conserved compared to the rest of the genome, so differences in the 5' UTR tend to be significant rather than just random variation. However, differences between BVDV1 and BVDV2 exist throughout the genome. The existence of two genotypes is significant because there are antigenic differences. The earliest isolations of BVDV2 strains were as vaccine escapes. Differences in acute pathogenesis may exist between the genotypes. Severe acute (SA) disease has only be reported with BVDV2 strains. However, it should be noted that BVDV2 strains causing SA are in the minority and most BVDV2 strains are no more virulent that BVDV1 strains. BVDV's may also exist as one of two biotypes, cytopathic and noncytopathic. It is thought that cytopathic viruses arise from noncytopathic viruses. This switch is frequently associated with the insertion of host or viral sequences into the viral genome. Biotype is not correlated with antigenic variation or pathology in acute infections. Biotype is important in persistent infections. Persistent infections have only been reported with noncytopathic viruses. Persistently infected animals superinfected with a cytopathic BVDV may succumb to mucosal disease.

3 PERSISTENT BOVINE VIRAL DIARRHEA VIRUS INFECTIONS Kenny V. Brock Auburn University, Auburn, Alabama Bovine viral diarrhea virus is a pathogen that is uniquely adapted to cattle by its' ability to cause the development of persistent fetal infections following in utero infections within the first 150 days of gestation. Control and prevention measures for BVDV have centered around the identification and removal of persistently infected animals and the judicious use of BVDV vaccines. To significantly reduce the prevalence of BVDV infection, immunization must prevent in utero infections against antigenically diverse BVDV. Understanding the requirements for fetal protection will aid in improved control. It is the unique pathogenesis of BVDV that gives it a selective advantage allowing continual mutation and antigenic variation within the cattle population. Therefore, BVDV has become widespread while being responsible for accumulative economic losses due to respiratory, reproductive and enteric disease in the cattle population. It is clear that vaccination (modified-live or killed) can provide a certain level of protection from acute disease and the development of persistently infected fetuses in vaccinated cows. However, it is also clear that vaccination programs alone cannot control or eliminate BVDV. In naturally exposed herds and vaccinated herds, BVDV infections are not self-limiting and may persistent in herds over time. This underscores the ability of the BVDV genome to remain fluid under selective pressures. Removal of persistently infected animals via a control program will consequently make it clear that protection afforded by vaccination is a key factor in the success of prevention.

4 ASSESSMENT OF BVDV CONGENITAL INFECTION IN DRY-LOT DAIRY CATTLE UNDER FIELD MANAGEMENT CONDITIONS Claudia Munoz-Zanzi, 1 * Sharon Hietala, 2 Mark Thurmond, 1 Wes Johnson 3 1 Department of Medicine and Epidemiology, University of California, Davis. 2 California Animal Health and Food Safety Laboratory, Davis. 3 Department of Statistics, University of California, Davis. Fetal infection with BVDV resulting in apparently normal calves with no persistent infection (PI), defined here as congenital infection (CI), has been described experimentally but generally not been considered to represent a herd health problem. A field study was used to characterize risk factors and assess potential long-term health effects of CI in 2 herds practicing routine BVDV vaccinations and showing no clinical signs of BVDV infection. Fetal infection was identified in approximately 10% of the calves, 0.5% with PI and 9.6% with CI. A higher probability of CI was associated with high dam BVDV type II titers at calving and with dam parity, dependent on the herd. CI was associated with a detrimental effect on calf health, identified as increased risk of a severe morbid episode. Decreased fertility at first breeding was additionally identified for CI heifers also infected with other specified pathogens. Results of the current work emphasize the need for further studies aimed at understanding the occurrence and significance of CI under field conditions.

5 BVDV IMMUNITY AND MATERNAL ANTIBODY Janice Endsley University of Missouri- Columibia Bovine viral diarrhea virus (BVDV) contributes significantly to health related economic losses in the beef and dairy industry. The emergence of strains that cause more severe disease in young calves has generated interest in protecting calves from acute BVDV infection at an earlier age than previously considered necessary. Antibodies of maternal origin are protective against BVDV infection, however, calves with low titers of maternal antibody or that do not receive colostrum may be at risk for acute BVDV infection. Interference by maternal antibodies prevents the development of an antibody response following vaccination with either a killed or attenuated BVDV vaccine. However, the T cell mediated immune response to BVDV may be generated in the absence of a detectable serum neutralizing antibody response. Two trials were conducted to evaluate the potential to elicit T cell mediated immune responses to BVDV in calves with circulating maternal antibody to BVDV. In the first trial, calves with high levels of circulating maternal antibody to BVDV 1 and BVDV 2 were experimentally infected with BVDV 2 (strain 1373) at 2-5 weeks of age. The T cell mediated immune responses of the experimentally infected calves and non-infected calves were monitored monthly until circulating maternal antibody was no longer detectable in either treatment group. Calves experimentally infected with BVDV developed BVDV specific CD4+, CD8+, and (( T cell responses while high levels of maternal antibody were circulating. A second challenge with BVDV 2 (strain 1373) was performed in the experimentally infected and control calves once maternal antibody could no longer be detected. Previous exposure to BVDV in the presence of maternal antibody protected calves from clinical signs of acute BVDV infection compared to the control calves. In the second trial, three groups of calves with circulating maternal antibody to BVDV were given either a modified live vaccine (MLV) containing BVDV 1 and BVDV 2, a killed vaccine containing BVDV 1 and BVDV 2, or no vaccine, at 7 weeks of age. Serum neutralizing antibody levels and antigen specific T cell responses were monitored for 14 weeks following vaccination. Calves vaccinated with MLV BVDV developed BVDV 1 and BVDV 2 specific CD4+ T cell responses, and BVDV 2 specific (( T cell responses, in the presence of maternal antibody. Vaccination with killed BVDV did not result in the generation of measurable antigen specific T cell immune responses. In this trial, a second vaccination was performed at 14 weeks to determine whether an anemnestic antibody response could be generated when calves were vaccinated in the presence of maternal. Calves vaccinated with either a MLV or killed BVDV vaccine while maternal antibody circulated developed a memory antibody response to BVDV 2 upon subsequent vaccination. The results of these trials indicate that vaccinating young calves for BVDV while maternal antibody is present generates T cell mediated immunity to BVDV.

6 THE CYTOKINE RESPONSE TO BVD VIRUS Ernst Peterhans Institute of Veterinary Virology, University of Bern, Switzerland BVD virus is unique in causing two fundamentally different types of infection: acute-transient in immunocompetent animals and persistent in animals infected early in their intrauterine development. Acute-transient infection can be caused both by cytopathic and non-cytopathic biotypes of BVD virus whereas persistent infection is due to the non-cytopathic biotype only. The persistence of BVD virus is associated with immunotolerance that extends to both the humoral and cellular arms of the immune system. In general terms, immunotolerance is explained by the early time point of infection of the fetus, i.e. between days 40 and 120 of gestation. However, keeping in mind that key mechanisms of the innate immune system, in particular the capacity to produce interferon, are implemented from the earliest time point of development, it seems likely that virus will be confronted with this part of antiviral defense already during the period where persistent infection is established. In accordance with the failure to cause persistent infection, we have recently observed that BVD viruses of the cytopathic biotype readily induce interferon type I in macrophages whereas non-cytopathic BVD viruses do not activate this cell response. Since type I interferon is a key cytokine activating the specific immune response, we proposed that this difference may be crucial to the establishment of persistent infection. Indeed, Charleston and coworkers recently reported that fetuses experimentally infected with non-cytopathic BVD virus fail to produce interferon whereas those infected with cytopathic biotypes readily do (Charleston et al., (2001), J. Gen. Virol. 82,1893). Pointing to specific interference with interferon induction, cells infected with non-cytopathic BVD virus are resistant to exogenously added or transfected double-stranded RNA, a key viral signal triggering interferon production and apoptosis. As shown in Table 1, cp and ncp BVD viruses also influence numerous other functions of macrophages. In addition, work by Roth, Kaeberle and others in the late 70's and early 80's demonstrated that BVD viral infection affects various functions of lymphocytes, neutrophils and alveolar macrophages. Most of these alterations can be linked to the well-known immunosuppressive effects associated with BVD. Table 1: Effects of in vitro infection with BVD virus on bovine M( functions (=: no effect compared to mock, 8: enhanced, 9: reduced). Effect Ncp BVDV Cp BVDV Reference IFN type-1 synthesis = 8 Adler et al., 1997 Perler et al., 2000 Induction of apoptosis = 8 Schweizer & Peterhans 1999 Prostaglandin E 2 synthesis = 8 Van Reeth & Adair, 1997 No synthesis after LPS or S. dublin treatment 8 9 Adler et al., 1994 TNF-α synthesis after LPS treatment 9 9 Adler et al., 1996 Superoxide production induced by PMA 9 9 Adler et al., 1994 Procoagulant activity induced by S. dublin = = Adler et al., 1994 IL-1 inhibitor activity induced by LPS 8 8 Jensen & Schulz 1991

7 Cytokine-induced chemotaxis 9 9 Keterlsen et al., 1979 Finally, as yet undefined factors (probably cytokines) released from cells infected with cytopathic BVD virus in conjunction with LPS may in part explain the typical location of the lesions of mucosal disease. Thus, macrophages infected with cytopathic biotypes of BVD virus were shown to release factor(s) priming uninfected macrophages for apoptosis upon exposure to LPS (Adler et al., 1997; Perler et al., 2000), a constituent of the cell wall of gram-negative bacteria that abound in the gastrointestinal tract.

8 USE OF SERIAL ANALYSIS OF GENE EXPRESSION TO MEASURE CHANGES IN GENE EXPRESSION IN BVDV2-INFECTED MDBK CELLS John D. Neill National Animal Disease Center, USDA, ARS, Ames, IA Noncytopathic BVDV has the ability to establish non-apparent, persistent infections in both cell culture and in calves infected in the first trimester of pregnancy. The mechanism of development of tolerance of the infecting virus is unknown. To better understand the interactions of the host cell and virus, serial analysis of gene expression (SAGE) was used to develop a global picture of cellular events that take place following infection. Use of SAGE allows quantitation of virtually every transcript in a cell type without prior sequence information. Comparison of the SAGE data obtained from both noninfected and BVDV2-infected cells revealed a number of cellular changes that could be placed into distinct categories. Most obvious was the finding that the expression levels of both alpha and beta-tubulins were decreased, indicating potential cell division aberrations. Also showing lowered expression levels were genes encoding proteins involved in energy production and those critical for cap-dependent protein translation initiation. Expression of a number of genes involved in downstream protein translation and modification were upregulated. This included those involved in increasing translation efficiency and in nascent peptide transport into the endoplasmic reticulum. Many, but not all of the changes in gene expression that were observed were beneficial to the virus while placing the cell at a metabolic disadvantage.

9 LESIONS AND TISSUE DISTRIBUTION OF VIRAL ANTIGEN IN SEVERE ACUTE VERSUS SUBCLINICAL ACUTE INFECTIONS WITH BVDV2 E.M. Liebler-Tenorio 1 *, J.F. Ridpath 2, J.D. Neill 2 1 *Department of Pathology, Veterinary School Hannover, Germany, 2 NADC, USDA-ARS, Ames, Iowa, USA Differences in the distribution and spread of viral antigen, development of lesions and correlation between presence of viral antigen and lesions were compared between an avirulent and virulent strain of BVDV2. Two groups of 2-week- to 2-month-old colostrum-deprived calves were intranasally inoculated with the naturally occurring avirulent BVDV2 strain or the virulent strain To study the sequence of virus spread and lesion development, calves were necropsied at days 3, 6, 8/9 and 12 to 14 post inoculation (pi). Viral antigen was detected by the indirect immunoperoxidase method in cryostat sections and lesions were evaluated in H&E-stained paraffin sections. Clinical signs and changes in lymphocyte and thrombocyte numbers confirmed the difference in virulence between the two strains. The avirulent and virulent strain showed comparable initial infection and spread at day 3 pi. At day 6 pi, both strains were found widespread in lymphoid tissues and multifocally in intestinal mucosa. Lesions were very mild despite the large amount of antigen in the lymphoid tissues. After day 6 pi, differences between the avirulent and virulent strain became more prominent. The avirulent strain was cleared from the tissues, but there was a transient phase of depletion. The virulent strain continued to spread to different organs and there was severe depletion of lymphoid tissues without recovery.

10 BVDV SEROLOGY Chris Chase Dept. Vet. Sci., SDSU, Brookings, SD Bovine viral diarrhea virus (BVDV) continues to be a major problem and serology remains an important tool for BVDV diagnosis and control. BVDV serology tests represent the largest number of bovine samples that are analyzed at the Animal Disease Research and Diagnostic Laboratory at SDSU. A number of different formats are available including ELISA and serum neutralization. Serology has been used as a regulatory tool for disease control, an epidemiological tool for estimating the prevalence of a disease and a management tool for accessing disease control strategies in a herd. BVDV serology been used proactively in herds to screen the pathogen exposure of potential breeding stock (health matching) or as a preprogrammed series of regular tests to determine proper vaccination times. The level and duration of BVDV titers are useful for examining exposure and vaccination responses. BVDV serology has many caveats including using serology as the sole diagnostic technique.

11 DIAGNOSTIC TESTING PROGRAMS ARE BUT ONE ELEMENT OF A BVDV CONTROL PROGRAM Or I haven't Gotten Very Far in 20 Years Simply Testing Cows Edward J. Dubovi Animal Health Diagnostic Laboratory at Cornell The challenge which still exists over 50 years after the first clinical descriptions of BVDV infections in cattle is to develop effect means to control the virus in the bovine population. Over the past 20 years, a variety of diagnostic tests have been developed which when properly applied can accurately detect the presence of BVDV in an animal or in a herd. The continued economic losses sustained by the presence of BVDV in herds are not the fault of the tests available. Tests are no longer the issue, but testing programs are. Available diagnostic tests will be discussed and their application in control programs will be presented. The intersections of immunization programs with testing programs and biosecurity will emphasized. The provision of legendary testing services while a necessary element in the control of BVDV is not sufficient in the absence of a verifiable farm management program.

12 No abstract available at time of printing. BVDV AND BIOLOGICS Randall Levings USDA APHIS CVB-L

13 ECONOMIC IMPACT OF BVDV INFECTION IN DAIRIES Hans Houe Department of Animal Science and Animal Health, Veterinary Epidemiology The Royal Veterinary and Agricultural University, Frederiksberg C, Denmark The detrimental effects of BVDV infections on health and production include reduced milk production, reduced reproductive performance, growth retardation, increased occurrence of other diseases, unthriftiness, early culling and increased mortality among especially young stock. These losses have been documented in several case descriptions and to some extent quantified in epidemiological studies. The detrimental effects have together with information on population structure, incidence of infection and monetary value of production losses been included in different models for estimating the economic losses and for comparing the economics of different control strategies. This paper reviews different studies and methods for estimating economic losses and effect of control strategies on both the herd level and the national level. The estimated losses in individual herd outbreaks have varied from a few thousand up to 100,000 $ per herd. There seems to be no universal truth for the economic most optimal strategy at the herd level as it depends on herd specific conditions. Most estimations of the losses at the national level range between 10 and 40 million $ per million calvings. In a few countries having introduced eradication campaigns, the programs have shown to be cost effective. However, selection of control strategy should always rely on thorough epidemiological investigations in the same areas as in which the program is going to be applied.

14 BOVINE VIRAL DIARRHEA VIRUS ANTIGENIC DIVERSITY: IMPACT ON DISEASE AND VACCINATION PROGRAMS Robert W. Fulton Dept of Vet Pathobiology, College of Vet Med, Stillwater, OK Bovine viral diarrhea virus (BVDV) is present in the U.S. and other cattle producing countries worldwide. BVDV is responsible for numerous clinical cases, including acute infections with respiratory tract disease, digestive tract disease, and conditions associated with the immunosuppressive effects of the viral infection. Fetal infections are an important manifestation of BVDV, particularly when susceptible pregnant heifers/cows develop a viremia after the initial acute infection. There are several outcomes resulting dependent on gestational stage when the fetus is exposed: abortions, congenital anomalies, and newborn calves born immunotolerant to the BVDV and persistently infected (PI) throughout their lifetime. While animals acutely infected shed BVDV potentially exposing susceptible contact cattle, the PI animals are considered the principal reservoir or source of infection. Thus considerable emphasis is placed on the identification and removal of PI animals from the herd. Procedures such as immunohistochemistry to detect BVDV antigen in skin biopsies and viral isolations from blood leukocytes or serum (two positive tests 3-4 weeks apart) are important diagnostic laboratory procedures in the BVDV control programs to identify PI animals. BVDV are classified as biotypes and genotypes. The biotypes are based on presence or absence of visual cytopathic effects in infected cell cultures: cytopathic (CP) or noncytopathic (NCP). The genotypes are based on nucleic acid differences in the viral genome based on PCR of specific region as well as genomic sequencing. There are also antigenic differences associated with the genotypes. The predominant genotypes in U.S. cattle are BVDV1 and BVDV2. However there are subtypes of BVDV1 represented by BVDV1a and BVDV1b. The impact of different subtypes of each genotype has implications for diagnostic tests using antigenic differences as well as disease control via vaccines. There are antigenic differences between BVDV1a and BVDV1b. The prevalence of BVDV CP and NCP biotypes and BVDV1 and BVDV2 genotypes were determined from BVDV positive samples from bovine accessions to a diagnostic laboratory. Of the 105 BVDV samples there were 26 type 1 BVDV CP strains (24.8%) 38 type 1 NCP strains (36.2%), 10 type 2 CP strains (9.5%) and 31 type 2 NCP strains (29.5%). NCP biotypes were isolated more frequently, 65.7% than CP biotypes, 34.3% and type 1 genotypes were more frequently isolated, 61%, than type 2 genotypes, 39%. There were 14 BVDV isolates from cattle previously vaccinated with modified live virus (MLV) or killed vaccines. Cattle with respiratory disease history had more NCP than CP biotypes, and more type 1 than type 2 genotypes. There were 41 of the 64 BVDV1 genotypes subtyped by differential PCR and genomic sequencing with 68.3% BVDV1b subtype and 31.7% BVDV1a subtype. In recent studies, BVDV1b was the predominant BVDV subtype isolated from calves with respiratory disease. The role of BVDV in feedlot performance was evaluated in a retained ownership program whereby calves from ranches received selected vaccines prior to delivery. The calves were sampled at delivery prior to entering the feedyard and with nasal swabs and blood collected for bacterial and viral isolation, along with serums. Serums were assayed for antibodies to selected pathogens. The calves were monitored for illness during the feeding period, and the calves were evaluated for various parameters at the completion of the feeding. The carcass evaluation was performed at processing. There were predictors of illness and production parameters. These included antibodies to selected pathogens in serums from calves entering the feedyard. Herds with low morbidity had higher BVDV1 antibodies

15 than herds with high morbidity. Calves with low BVDV1 and BVDV2 antibody titers had increased treatment costs. Calves with lower BVDV1 and BVDV2 antibody had a decreased net to owner (carcass value minus total costs in feedyard). Calves treated twice or more had lower BVDV1 serum antibody levels than those treated once or not at all. There are both MLV and killed BVDV vaccines available in the U.S. for BVDV control. Until recently the U.S. vaccines contained only BVDV1a strains such as the Singer, NADL, or C24V Oregon strains. Now there are licensed BVDV vaccines, both MLV or killed, containing BVDV2. There is only one licensed vaccine containing BVDV1b, the NCP New York-1 strain. Licensing of U.S. vaccines currently does not require specific challenge virus, although several studies have indicated BVDV1a challenge strain and in some cases a BVDV2 viral challenge. The question for BVDV vaccine efficacy would be "do BVDV1a vaccines provide protection against BVDV1b." To eradicate or control BVDV in cattle, there must be methods successfully implemented to eliminate the reservoir of BVDV infection in cattle, the PI animal. Currently by using IHC and viral isolation, PI cattle currently in the population can be identified. Elimination of new PI animals requires that the pregnant heifer/cow be protected from viremia leading to fetal infection. There are U.S. studies reporting the protection induced by BVDV vaccine. The U.S. studies have indicated that a MLV vaccine containing a BVDV1a strain (NADL) given to susceptible heifers/cows prior to breeding, and challenged during pregnancy with either a BVDV1 strain or a BVDV2 strain has provided protection against fetal infections, however, the protection was not 100% complete and some of the fetuses/calves born to vaccinated females were infected. It is noteworthy that a limited number of U.S. BVDV vaccines have been evaluated for fetal protection. Ideally there will be efficacious BVDV vaccines developed and available, that when they are used appropriately, 100% of the susceptible females and their fetuses will be protected, thus eliminating the source of PI calves.

16 BOVINE VIRAL DIARRHEA VIRUS IN WILDLIFE Hana Van Campen Department of Microbiology, Veterinary Diagnostic Laboratory, Colorado State University, Fort Collins, CO Serologic and virologic findings indicate that a variety of North American wild ruminant species are infected with pestiviruses. Seroprevalences of greater than 50% suggest that BVDVs are maintained in free-ranging populations of mule deer, elk and bison. In addition, wild ruminants may harbor unique pestiviruses such as that found in pronghorn antelope. BVDVs are associated with infertility, abortions and neonatal losses in captive elk and bison, diseases similar to those observed in range cattle. Type 1a and 2 BVDVs have been isolated from free-ranging Wyoming mule deer without an observable impact on the health of these populations. On the Uncompahgre Plateau in Colorado, type 1 BVDV has been associated with increased mule deer fawn mortality in , and may represent a recent introduction of the virus into this population. Experimentally, BVDV is not transmitted from acutely infected deer to calves. The existence of PI deer has not been demonstrated; however, it is speculated that PI deer or aborted deer fetuses may serve as an efficient source of BVDV for cattle. The risk of transmission of BVDV from deer to cattle under range conditions is unknown. Cattle are assumed to be the source of BVDV infection for free-ranging ruminant species.

17 BVDV ERADICATION PROGRAMS IN EUROPE Irene Greiser-Wilke Institute of Virology, School of Veterinary Medicine Hannover, Germany The economic impact of BVDV infections has lead a number of countries in Europe to start eradication or control programs, respectively. 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. The first country to design and implement an eradication program was Sweden (1993), a country with a relatively low cattle density and low seroprevalence. For screening, an indirect antibody ELISA which can be used for serum, milk and bulk milk samples is being used. The basics of the Swedish model are: no vaccination, voluntary participation, the subscribing farmers finance the entire scheme, 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 The aim of control programs 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 State. Screening is performed using an antigen capture ELISA with blood or serum. If all animals in a herd which are up to 36 months old are negative for BVDV antigen, the herd is declared BVDV unsuspicious. After elimination of PI animals, heifers are vaccinated. In order to achieve maximum fetal protection an inactivated vaccine is used for basic immunization, and attenuated live virus for boostering.

18 BOVINE VIRUS DIARRHOEA VIRUS - STRATEGIC DECISIONS FOR CONTROL IN THE UK Joe Brownlie Royal Veterinary College, Department of Pathology and Infectious Diseases, Hawkshead Lane, North Mymms, Hatfield, Herts UK Bovine virus diarrhoea virus (BVDV) is, undeniably, one of the most important viral diseases of cattle. The paradox for diagnosis is that clinical signs range from the inapparant to either severe haemorrhagic disease or fatal mucosal disease whilst the immunosuppressive effect of acute BVDV infections can enhance clinical disease from other pathogens. In recent years, there has been a growing awareness for its major role in reproductive loss; causing early embryonic loss, abortions and the birth of persistently viraemic calves. The laboratory tests for both BVDV and viral antibody are excellent. Detection of the persistently infected animal is a central part of all eradication strategies; however, many herds may benefit from a combined vaccination and eradication programme. The interpretation of antibody titres, as a basis for vaccination and control in these programmes, is complex. In the last decade, there has been a great explosion in our understanding of the molecular mechanisms of viral replication and mutation, especially those related to biotypic variation. There has also been a greater understanding, amongst farmers and veterinary practitioners, of the importance of BVDV as a primary pathogen of cattle disease. BVDV vaccines are widely available in the UK thereby giving better prospects for protection against infection. However, for the veterinary clinician, it is the strategic decisions of diagnosis, control, vaccination and possibly eradication for BVDV that remain the difficult responsibility. It is these dilemmas within the UK that I shall discuss. POSITION STATEMENT ON BOVINE VIRAL DIARRHEA VIRUS ACADEMY OF VETERINARY CONSULTANTS APPROVED BY MAJORITY VOTE OF MEMBERSHIP, NOVEMBER, 2001 The beef and dairy industries suffer enormous loss due to effects of bovine viral diarrhea virus (BVDV) infection. The highly mutable nature of BVDV and the emergence of highly virulent strains of BVDV contribute to limited success of present control programs. Also, persistently infected cattle are the primary source of infection and effective testing procedures are available to identify those infected carriers. Therefore, it is the resolve of the Academy of Veterinary Consultants that the beef and dairy industries adopt measures to control and target eventual eradication of BVDV from North America.