David O. White

Immunization against Viral Diseases

The methods of reducing the impact of viral infections on animals of economic importance include a range of management practices such as test and slaughter, hygiene and sanitation, and immunization. The most generally applicable way of preventing viral diseases is by immunization, and the control of a large number of diseases of animals by immunization is the outstanding achievement of veterinary medicine in this century. The field has been catapulted to a new plane of promise by the application of new technologies including the use of recombinant DNA, site-directed mutagenesis, synthetic peptides, and bacterial, yeast, and mammalian expression systems. There are important differences between immunization practices in humans and animals. Except in developing countries, an economic constraint is of little importance in human medicine but is very important in most areas of veterinary practice. There is far greater agreement within and between countries about the safest and most efficacious vaccines to be used in human vaccination than there is with vaccines destined for use in animals. Viral vaccines have traditionally been classified into two broad categories: live-virus and inactivated. Most live-virus vaccines are attenuated mutants selected for their relative avirulence.

Togaviridae and Flaviviridae

The term arbovirus (arthropod-borne virus) is used without taxonomic implication to describe any virus that is perpetuated in nature by replication cycles involving hematophagous arthropod hosts and vertebrate hosts. The earliest attempts to classify the large number of viruses found to be transmitted by arthropods utilized serological tests. Later, as physicochemical and morphological data confirmed the fundamental basis of serological relationships, two major serogroups, which had been called the group A and group B arboviruses, were designated as the genera Alphavirus and Flavivirus , respectively, within the family Togaviridae . Other serogroups and serologically unrelated arboviruses were allocated to the families Bunyaviridae , Rhabdoviridae , and Reovir . Some non-arthropod-borne viruses were then found to have physicochemical characteristics similar to those of the arthropod-borne members of the family Togaviridae and so were included in this family within the genera Rubivirus , Pestivirus , and Arterivirus . As the great majority of togaviruses and flaviviruses are arthropodborne, it is necessary to recall some of the essential features of the life cycles of arboviruses, in respect of their disease potential in domestic animals. Most have localized natural habitats in which specific arthropod and vertebrate hosts allow them to fulfill their life cycle.

Laboratory diagnosis of viral diseases

Publisher Summary Tests for the specific diagnosis of a viral infection in an animal are of two general types: (1) those that demonstrate the presence of the virus and (2) those that demonstrate the presence of specific viral antibody. The provision, by a single laboratory, of a comprehensive service for the diagnosis of viral infections of domestic animals is a formidable undertaking. There are about 200 individual viral species in some 20 different viral families that infect the eight major domestic animal species. If antigenic types within an individual viral species are considered and the number of animal species is broadened to include turkey, duck, and zoo and laboratory animals, then the number of individual viruses exceeds 1000. It is, therefore, not surprising that few single laboratories could have available the necessary specific reagents, skills, and experience for the diagnosis of such a large number of infections.

Viral Genetics and Evolution

Animal virology developed largely from the need to control viral diseases in humans and their domesticated animals. As direct experimentation using the natural host is often expensive or impossible, much effort has been devoted to two ends: (1) the adaptation of viruses of veterinary and medical importance to small laboratory animals and cell culture and (2) the attenuation of viruses by serial passage in an unnatural host to obtain attenuated live-virus vaccines. These processes of adaptation and attenuation operate via spontaneous mutation or more rarely by genetic recombination, followed by selection. As is usual in science, useful practical results were obtained empirically long before the genetic or molecular mechanisms involved in these phenomena were understood. This is well illustrated by the development of an effective attenuated rabies vaccine by Pasteur a hundred years ago. At present, however, it is possible and important to understand what these processes are and how they occur. Following the spectacular advances in molecular genetics that emerged from the study of bacterial viruses, and later, tumorigenic viruses, efforts have been made to understand the genetic properties and processes of other animal viruses. This work has involved the selection of appropriate mutants, the construction of genetic maps by recombination and complementation tests, and the study of the functions of the products of the genes in which mutations occur.

Cultivation and Assay of Viruses

Publisher Summary Viruses replicate only within living cells. Some viruses are restricted in the kinds of cells in which they replicate, and a few have not yet been cultivated at all under laboratory conditions. However, most viruses are grown in cultured cells, embryonated hens eggs, or laboratory animals. In veterinary virology, the natural host animal is used for the cultivation of viruses; indeed the earliest viral assay has been carried out with foot-and-mouth disease virus in cattle. The natural host is still useful for the studies of pathogenesis and immunology, experiments in chemotherapy, and occasionally for diaglostic purposes. However, the in vitro cultivation of viruses in cell cultures is essential for the study of their mode of replication and for diagnostic virology. Cells may be grown in vitro as explants of tissue, such as respiratory or intestinal epithelium, or as cell cultures. Explant cultures are occasionally used for research purposes or for the cultivation of certain viruses, but almost all diagnostic and research work involving viral cultivation is carried out in cell cultures—usually in monolayers, occasionally as suspension cultures. To produce cell monolayers, tissue is cut into small pieces and placed in a medium containing a proteolytic enzyme such as trypsin. After the cells have dispersed into a single-cell suspension, they are washed, counted, and diluted in a growth medium and permitted to settle on the flat surface of a glass or plastic container. Most types of cells adhere quickly and under optimal conditions, they divide about once a day until the surface is covered with a confluent monolayer.

Epidemiology of Viral Infections

Publisher Summary Viruses survive in nature only if they are able to pass from one host to another, whether of the same or another species. Viral epidemiology is the study of the factors that determine the frequency and distribution of viral diseases in an animal population. In the broadest sense, epidemiology may be viewed as a part of population biology, involving not only environmental factors but also genetic factors in both the virus and the host. The terms incidence and prevalence are used to describe quantitative aspects of the occurrence of infections in populations. The incidence of infection is defined as the proportion of a population contracting that infection during a specified period, whereas prevalence refers to the proportion infected at a particular point in time. The comparisons of incidence and prevalence at different times and places are made by relating the appropriate numerator to a denominator that may be as general as the total population of the animal species concerned or may be specified as the susceptible population at risk. A disease is said to be enzootic when there are continuous chains of transmission in the region involved; epizootics are peaks in disease incidence. The size of the peak required to constitute an epizootic is arbitrary and is related to the background enzootic rate, the morbidity, and the anxiety that the disease arouses.

Structure and Composition of Viruses

Publisher Summary Viruses are smaller and simpler in construction than unicellular microorganisms, and they contain only one type of nucleic acid—either DNA or RNA—never both. As viruses have no ribosomes, mitochondria, or other organelles, they are completely dependent on their cellular hosts for energy production and protein synthesis. They replicate only within cells of the host that they infect. Unlike any microorganism, many viruses can, in suitable cells, reproduce themselves from their genome, a single nucleic acid molecule, that is, their nucleic acid alone is infectious. Outside a susceptible cell, the virus particle like a bacterial spore is metabolically inert; on the other hand, when replicating in a cell, it exhibits all the characteristics of life. The new group of microorganisms are known as the filterable viruses. The filtration studies has shown that virus particles (virions) range from about the size of the smallest unicellular microorganisms (300 nm) down to objects little bigger than the largest protein molecules (20 nm). In the simpler viruses, the virion consists of a single molecule of nucleic acid surrounded by a protein coat, the capsid; the capsid and its enclosed nucleic acid together constitute the nucleocapsid.

Mechanisms of Persistent Infections

Viruses of some families, notably the herpesviruses, have long been known to cause infections that usually persist for the life of the animal, although the episodes of clinical disease might occur infrequently and at long intervals. Viruses have been found to be responsible for many chronic diseases in which virus persists for months or for life and causes continuing, often subtle, pathological effects. These persistent viral infections are important for four reasons: (1) they are often of epidemiological importance, as a source of infection of other animals, and provide a mechanism for the maintenance of the virus in nature; (2) they may be reactivated and cause acute episodes of disease; (3) they may lead to immunopathological disease; and (4) they may lead to neoplasia. Persistent infections of one type or another are produced by viruses of all families; indeed in veterinary medicine, acute self-limiting infections seem to be the exception rather than the rule, apart from the viral diarrheas and most viral respiratory infections. As in cultured cells, such infections may be characterized by the continuous or intermittent production of infectious virus or by the persistence of the viral genome either as provirus or as an episome. Some viruses, characteristically the alphaherpesviruses, produce cytocidal infections in most cultured cell systems but persistent as well as cytocidal infections in vivo .

The Immune Response to Viral Infections

Vertebrates differ from other organisms in having evolved the capacity to respond in a highly specific way to foreign macromolecules by means of what is called the immune system. Foreign macromolecules including viral components that activate this system are called antigens; immunoglobulins that recognize these antigens specifically are called antibodies. There is a parallel cellular system in which antigenic stimulation leads to the selection and activation of specific lymphocytes; this is called cell-mediated immunity. The immune response, if rapid in onset, may terminate some viral infections before much damage has been done. Consequently, many viral infections are mild or even subclinical—they produce few or no signs of disease. However, for a variety of reasons, the immune system does not always function effectively. Some viruses are almost always lethal for particular hosts, others establish persistent infections, and sometimes the immune response is actually harmful, causing tissue damage in vital organ. The chapter discusses the role of the immune response in recovery from viral infection and resistance to reinfection.

Mechanisms of Viral Tumorigenesis

This chapter describes a benign tumor as a lump produced by abnormal cell proliferation which remains localized and does not invade adjacent tissue. A malignant tumor, in contrast, is usually locally invasive and may also be metastatic, that is, spread by lymphatic and blood vessels to other parts of the body. Such malignant tumors are often referred to as cancers. Malignant tumors of epithelial cell origin are known as carcinomas, those arising from cells of mesenchymal origin as sarcomas, and those from lymphocytes as lymphomas or leukemia. The process of development of tumors is termed tumorigenesis, synonyms for which are oncogenesis and carcinogenesis. The capacity to study tumorigenesis at a molecular level has been facilitated when it became possible to induce essential genetic changes in cultured cells. Since the discovery of the viral etiology of avian leukemia, there has been a steady stream of discoveries clearly incriminating viruses in a variety of benign and malignant tumors of numerous species of mammals, birds, amphibia, and reptiles. Many retroviruses and a few herpesviruses cause malignant tumors under natural conditions, while papillomaviruses of many species of animals produce benign tumors, which may become malignant in cattle, rabbits, and humans.