Bovine Viral Diarrhea Virus Diagnosis, Management, and Control

Sagar M. Goyal, BVSc, MSC, PhD, Professor, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul.

Julia F. Ridpath, PhD, Virus and Prion Diseases of

Livestock Research Unit, NADC/ARS/USDA, Ames,

Iowa.

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First edition, 2005

Library of Congress Cataloging-in-Publication Data

Bovine viral diarrhea virus : diagnosis, management, and control / edited by Sagar M. Goyal and Julia F. Ridpath.— 1st ed.

p. cm.

Includes bibliographical references and index. ISBN 0-8138-0478-7 (alk. paper)

1. Bovine viral diarrhea virus. 2. Bovine viral diarrhea. I. Goyal, Sagar M., 1944II. Ridpath, Julia F.

SF967.M78B68 2005 636.2 08963427—dc22

2004029262

The last digit is the print number: 9 8 7 6 5 4 3 2 1

The disease caused by bovine viral diarrhea virus (BVDV) was first described in 1946, along with virus isolation from sick cattle. In the intervening 60 years, many important advances have been made in understanding this virus and the disease it produces. These developments include the recognition of BVDV biotypes and genotypes; development of monoclonal antibodies (Mabs) to study strain variation; defining the mechanism of development of persistent infections, mucosal disease, and immune tolerance; BVDV-induced immunosuppression; the discovery of problems caused by the presence of BVDV and anti-BVDV antibodies in fetal bovine serum used in the production of cell cultures; sequencing of viral genome; and the development of rapid methods for virus detection. These achievements have culminated in the development of control and eradication programs in several Scandinavian countries with some successes. Many other

countries, including the U.S., are contemplating eradication and/or control programs.

In spite of these developments and several symposia dedicated to discussing the pathogenesis, transmission, diagnosis, and molecular virology of the virus, BVDV and BVDV-induced diseases are not completely understood, as exemplified by the appearance of severe hemorrhagic disease caused by BVDV 2 in the early 1990s in Canada and then in other countries. It is with this in mind that we have attempted to collate information on the current state of knowledge on the diagnosis, management, and control of the multifaceted diseases caused by BVD viruses. An internationally renowned team of experts has been assembled to contribute chapters on various aspects of this problem.

We thank Dede Pedersen of Blackwell Publishing for keeping the book on track.

In 1996, Cornell University held an international symposium at the College of Veterinary Medicine. This event was a celebration of 50 years of bovine viral diarrhea virus (BVDV) research marked from the time of the first publication on BVDV, “An apparently new transmissible disease of cattle,” by Cornell University researchers (Olafson et al., 1946). Presenting at the meeting were two Cornell pioneers: Dr. Francis Fox, one of the coauthors of the original publication, and Dr. James Gillespie who, with his colleagues, had propagated the first isolates of BVDV in tissue culture. Also presenting at this meeting was another BVDV pioneer, Dr. Bernd Liess of the Hannover Veterinary School, who recounted his early experiences and interactions with Cornell University researchers. Their historical perspectives on the discovery of the disease, the virus, and the scientific contributions of Cornell University are recorded (Fox, 1996; Gillespie, 1996; Liess, 1996). These personal accounts are highly recommended reading. The meeting was a blend of “old” and “new.” Classical (type 1) BVDV was now 50 years old, but what dominated the discussion was the newly discovered genotype of BVDV (type 2 BVDV) and the disease it causes.

From its emergence as a new virus in 1946 to the present day, BVDV has proven to be multifaceted in the disease it produces and is arguably the most complicated bovine virus in its pathogenesis. During the past half-century and more, a multitude of advances have been made in BVDV research and diagnostics. These advances have led to the development of numerous diagnostic tests and the design of successful management and control strategies for BVDV. The discovery of persistent infection and how this state is produced in cattle was key to both our understanding of how BVDV maintains itself and to developing rational control and eradication strategies.

Vaccines were first mass produced in the 1960s to deal effectively with the acute disease but were also found to occasionally precipitate a severe manifestation of BVDV called mucosal disease (MD). The pathogenesis of spontaneous and vaccine-induced mucosal disease in persistently infected cattle came to be understood by important discoveries in the 1960s and 1980s. The decade of the 1980s also saw the first complete sequencing of a BVDV genome and the production of monoclonal antibodies to the virus. These developments led eventually to new nucleic acidand monoclonal antibody-based diagnostic methods.

In the 1990s, virulent strains of a new BVDV genotype, type 2 BVDV, devastated many North American herds and presented yet another challenge for researchers, veterinarians, and vaccine companies. At the same time, several European countries embarked on eradication programs for BVDV without vaccination. These programs have been highly successful to date. Thus, in the beginning of the new millennium, countries and regions with endemic BVDV will need to consider what type of control programs, if any, they will embark on and what the costs and risks are. In the absence of national or regional programs, veterinarians and cattle producers need to know how to apply proper management and control strategies for individual herds. The objective of this book is to provide detailed information on our current knowledge of the virus and the diseases it causes, the diagnostic methods available, and management systems.

In writing this chapter on the history of BVDV, the author has divided the historical developments into specific time periods. However, to avoid too much fragmentation of thought, some related developments, that either overlap the time periods (earlier or later) or may be too brief to mention individually in their time period, may be brought together in a

single context in the period in which the most significant findings or a majority of the research took place. These events are referenced with their date of publication and, thus, should not be confusing to the reader. In addition to providing a history and introduction to the virus and disease, another objective in writing this chapter is to provide an introduction (in historical context) of subjects that are further developed in subsequent chapters.

THE EARLY YEARS, 1946–1969

THE VIRUS AND THE DISEASE

The new transmissible disease in cattle, described by Cornell University researchers Olafson, MacCallum, and Fox (1946), was characterized by leukopenia, high fever, depression, diarrhea and dehydration, anorexia, salivation, nasal discharge, gastrointestinal erosions, and hemorrhages in various tissues. Initially, the disease was observed in Ithaca, New York, in a “one-cow herd” by Dr. Francis Fox, who initially considered the disease to be classical winter dysentery in his recounting of the event (Fox, 1996). Subsequently, outbreaks of the disease occurred in other herds in the area. In five initial herds, the morbidity ranged from 33–88% and mortality was 4–8%. In addition to other signs, milk production was diminished and fetal abortions occurred 10 days to 3 months following infection. Some of the cows in one herd developed pneumonia. The severe leukopenia seen in clinically affected animals was considered to be indicative of a viral etiology. The attempted treatment involved blood transfusions, but often the apparently healthy donor animals of the herd had a more severe leukopenia than the clinically affected animals (Fox, 1996). This indicated that the donors were infected and that BVDV infections could also be subclinical in nature.

The lesions of BVD resembled those of rinderpest, an exotic disease for the U.S. However, the disease observed by Olafson et al. (1946) did not behave as rinderpest. Since the U.S. had a susceptible cattle population, rinderpest would have presented a much more devastating clinical picture with high transmission and mortality rates. However, it was thought that a mild form of rinderpest could have been responsible for the lesions observed and, thus, it was important to rule out this disease. Subsequently, Walker and Olafson (1947) demonstrated experimentally that sera from cattle that recovered from BVD did not neutralize rinderpest virus and that these recovered cattle did not show resistance to infection with the rinderpest virus.

After the report of acute BVD in New York, a similar but more severe disease in cattle was reported in Canada by Childs (1946). This report was considered by Pritchard (1963) in his review of those early times as probably the first description of mucosal disease in cattle. Mucosal disease was characterized by fever, anorexia, depression, profuse salivation, nasal discharge; gastrointestinal hemorrhages, erosions, and ulcers; and severe diarrhea with watery feces that were sometimes mixed with blood. Lesions of the gastrointestinal tract were quantitatively much more severe in MD than those observed in BVD. Furthermore, MD usually affected only a few animals in a herd but had a very high case fatality rate. In 1953, Ramsey and Chivers (1953) reported on MD in the U.S. and gave the disease its name. These authors noted that MD had some of the characteristics of BVD but was apparently not transmissible experimentally, and only fever was observed in cattle inoculated with the agent. Thus, based on the differences in lesions of the gastrointestinal tract, the low morbidity and high case fatality rates, and the nontransmissibility of MD, it was thought to be a disease distinct from BVD.

It was discovered in 1957 that the viral agent isolated in acute BVD did not cause cytopathology in vitro, meaning that infected cells in culture appeared normal (Lee and Gillespie, 1957). In the same year, a cytopathic virus had been isolated from MD (which was thought at the time to be caused by a different virus than the one causing BVD) (Underdahl et al., 1957). After the isolation of two noncytopathic viruses from BVD cases, including the reference NY-1 strain (Lee and Gillespie, 1957), Gillespie et al. (1960) reported the first isolation of a cytopathic strain of BVDV, designated Oregon C24V. The discovery of cytopathic strains allowed the development of serum neutralization and plaque neutralization assays. Cytopathic strains could be more easily studied in tissue culture than noncytopathic strains, and their neutralization with antisera allowed characterization of the antigenic relatedness of viruses from cases of BVD and MD. Studies employing virus neutralization (Gillespie et al., 1961; Kniazeff et al., 1961; Thomson and Savan, 1963) determined that the viral agents isolated from BVD and MD in North America and Europe were, indeed, the same and that BVD and MD were actually different disease manifestations caused by the same agent. Thus, several years later, the disease became officially known as bovine viral diarrhea-mucosal disease (BVD-MD) (Kennedy et al., 1968).

In an early review of BVD-MD, Pritchard (1963)