Introduction: A Brief History of Animal Virology
The history of human development has been shaped by at least three major recurring elements: (1) environmental changes; (2) human conflicts; (3) infectious diseases. With regard to infectious diseases, the impact has been not only directly on the human population, but also on the food supply. The origins of veterinary medicine are rooted in efforts to maintain the health of animals for food and fiber production, and animals essential for work-related activities. Control of animal disease outbreaks was not possible until the pioneering work of the late 19th century that linked microbes to specific diseases of plants and animals. Many attribute the beginning of virology with the work of Ivanofsky and Beijerinck (1892ā1898) on the transmission of tobacco mosaic virus. Both scientists were able to show the transmission of the agent causing disease in tobacco plants using fluids that passed through filters that retained bacteria. Beijerinck also noted that the filterable agent could regain its āstrengthā from diluted material, but only if it were put back into the tobacco plants. The concept of a replicating entity rather than a chemical or toxin had its genesis with these astute observations. The era of veterinary virology had its beginning virtually at the same time as Beijerinck was characterizing tobacco mosaic virus transmission. Loeffler and Frosch (1898) applied the filtration criteria to a disease in cattle that later would be known as foot and mouth disease. Repeated passage of the filtrate into susceptible animals with the reproduction of acute disease firmly established the ācontagiousā nature of the filtrate and provided more evidence for a process that was inconsistent with toxic substances. These early studies provided the essential operational definition of viruses as filterable agents until chemical and physical studies revealed the structural basis of viruses nearly 40 years later.
In the early 20th century, use of the filtration criteria saw the association of many acute animal diseases with what were to be defined as viral infections: African horse sickness, fowl plague (high pathogenicity avian influenza), rabies, canine distemper, equine infectious anemia, rinderpest, and classical swine fever (hog cholera) (Table 1.1). In 1911, Rous discovered the first virus that could produce neoplasia (tumors), and for this discovery he was awarded a Nobel Prize. This early phase of virology was one of skepticism and uncertainty because of the limited tools available to define the filterable agents. Even with filtration, there were differences among the agents as to their size as defined by filter retention. Some agents were inactivated with organic solvents, whereas others were resistant. For equine infectious anemia, the acute and chronic forms of the disease were perplexing and an unresolved conundrum. These types of apparent inconsistencies made it difficult to establish a unifying concept for the filterable agents. For research on animal diseases, early workers were restricted to using animal inoculation in order to assess the impact of any treatment on any putative disease causing agent. For equine and bovine disease work, the logistics could be daunting. Help in providing definition to filterable agents came from the discovery of viruses that infected bacteria. Twort in 1915 detected the existence of a filterable agent that could kill bacteria. Like its plant and animal counterparts, the strength of a dilute solution of the bacterial virus could be regained by inoculating new cultures of bacteria. Felix dāHerelle also noted the killing of bacteria by an agent that he called ābacteriophage.ā He defined the plaque assay for quantitating bacteriophage, a technique that became a keystone for defining the properties of viruses and for the studies that became the basis of virus genetics.
Table 1.1
Selected Moments in the History of Virology
| Year | Investigator(s) | Event |
| 1892 | Ivanofsky | Identification of tobacco mosaic virus as filterable agent |
| 1898 | Loeffler, Frosch | Foot-and-mouth disease caused by filterable agent |
| 1898 | Sanarelli | Myxoma virus |
| 1900 | Reed | Yellow fever virus |
| 1900 | Mcfadyean, Theiler | African horse sickness virus |
| 1901 | Centanni, Lode, Gruber | Fowl plague virus (avian influenza virus) |
| 1902 | Nicolle, Adil-Bey | Rinderpest virus |
| 1902 | Spruell, Theiler | Bluetongue virus |
| 1902 | Aujeszky | Pseudorabies virus |
| 1903 | Remlinger, Riffat-Bay | Rabies virus |
| 1903 | DeSchweinitz, Dorset | Hog cholera virus (classical swine fever virus) |
| 1904 | CarrƩ, VallƩe | Equine infectious anemia virus |
| 1905 | Spreull | Insect transmission of bluetongue virus |
| 1905 | CarrƩ | Canine distemper virus |
| 1908 | Ellermann, Bang | Avian leukemia virus |
| 1909 | Landsteiner, Popper | Poliovirus |
| 1911 | Rous | Rous sarcoma virusāfirst tumor virus |
| 1915 | Twort, dāHerelle | Bacterial viruses |
| 1917 | dāHerelle | Development of the plaque assay |
| 1927 | Doyle | Newcastle disease virus |
| 1928 | Verge, Christofornoni Seifried, Krembs | Feline parvovirus (feline panleukopenia virus) |
| 1930 | Green | Fox encephalitis (canine adenovirus 1) |
| 1931 | Shope | Swine influenza virus |
| 1931 | Woodruff, Goodpasture | Embryonated eggs for virus propagation |
| 1933 | Dimmock, Edwards | Viral etiology for equine abortions |
| 1933 | Andrewes, Laidlaw, Smith | First isolation of human influenza virus |
| 1933 | Shope | Swine natural host of pseudorabies |
| 1933 | Bushnell, Brandly | Avian bronchitis virus |
| 1935 | Stanley | Tobacco mosaic virus (TMV) crystallized; protein nature of viruses confirmed |
| 1938 | Kausche, Ankuch, Ruska | First electron microscopy picturesāTMV |
| 1939 | Ellis, Delbruck | One step growth curveābacteriophage |
| 1946 | Olafson, MacCallum, Fox | Bovine viral diarrhea virus |
| 1948 | Sanford, Earle, Likely | Culture of isolated mammalian cells |
| 1952 | Dulbecco, Vogt | Plaque assay for first animal virusāpoliovirus |
| 1956 | Madin, York, McKercher | Isolation of bovine herpesvirus 1 |
| 1957 | Isaacs, Lindemann | Discovery of interferon |
| 1958 | Horne, Brenner | Development of negative-stain electron microscopy |
| 1961 | Becker | First isolation of avian influenza virus from wild bird reservoir |
| 1963 | Plummer, Waterson | Equine abortion virus=herpesvirus |
| 1970 | Temin, Baltimore | Discovery of reverse transcriptase |
| 1978 | Carmichael, Appel, Scott | Canine parvovirus 2 |
| 1979 | World Health Organization | WHO declares smallpox eradicated |
| 1981 | Pedersen | Feline coronavirus |
| 1981 | Baltimore | First infectious clone of an RNA virus |
| 1983 | Montagnier, Barre-Sinoussi, Gallo | Discovery of human immunodeficiency virus |
| 1987 | Pedersen | Feline immunodeficiency virus |
| 1991 | Wensvoort, Terpstra | Isolation of porcine reproductive and respiratory syndrome virus (PRRSV) |
| 1994 | Murray | Hendra virus isolated |
| 1999 | | West Nile virus enters North America |
| 2002 | | SARS outbreak |
| 2005 | Palase, Garcia-Sastre, Tumpey, Taubenberger | Reconstruction of the 1918 pandemic influenza virus |
| 2007 | | End of vaccination program for rinderpest |
| 2011? | | Declaration of the eradication of rinderpest |
The initial studies on tobacco mosaic virus led to further understanding of āfilterable agentsāānamely viruses. Specifically, the high concentration of virus produced in infected tobacco plants permitted the chemical and physical characterization of the infectious material. By the early 1930s, there was evidence that the agent infecting tobacco plants was composed of protein, and that antibodies produced in rabbits could neutralize the virus. The tobacco mosaic virus was crystallized in 1935, and in 1939 the first electron micrograph of a virus was recorded. The particulate nature of viruses was now an established fact. A further advance in animal virology was the use of embryonated eggs for culturing virus in 1931. In the same year, Shope identified influenza virus in swine; in 1933, influenza virus was isolated from human cases of the infection. The identification of the strain H1N1 in swine might be considered the first āemergingā disease in animalsāthat is, a virus crossing a species barrier and maintaining itself as an agent of disease in the new species. In an attempt to move away from large-animal experimentation, and to provide model systems for human diseases such as influenza, mice and rats became important tools for studying animal viruses. Thus we had the birth of laboratory animal medicine programs that have become the essential backbone of biomedical research.
The decade 1938ā1948 saw major advances by Ellis, Delbruck and Luria in the use of bacteriophage to probe the mechanism of inheritance of phenotypic traits of these bacterial viruses. Advances in understanding the properties of viruses progressed much more rapidly with bacterial viruses, because the work could be done in artificial media, without any requirement for laborious and time-consuming propagation of viruses in either animals or plants. A key concept in virus replication, namely the latent period, was defined using one-step growth curve experiments with bacteriophage. This observation of the loss of infectivity for a period after the initiation of the infection directed research to define the mode of replication of viruses as totally distinct from that of all other replicating entities. Animal virus studies made a dramatic shift in emphasis with the development of reliable in-vitro animal cell cultures (1948ā1955). As a result of intensive efforts to control poliovirus infections, single cell culture procedures were defined, cell culture media were standardized, a human cell line was developed, and growth of poliovirus in a non-neuronal cell demonstrated. These advances all permitted the development of a plaque assay for poliovirus 35 years after the concept was defined for bacteriophage. All the basic studies on animal viruses that were hindered by the necessity to work in animal systems were now possible, and the principles established for bacteriophage could be explored for animal viruses. The cell culture era of animal virology had begun.
The advances in virology driven by human disease control efforts were directly applicable to animal virology. Bovine viral diarrhea virus was identified as a new disease-causing agent in cattle in 1946 and by the late 1950s was considered the most economically important disease of cattle in the United States. Cell culture procedures permitted isolation of the virus and the production of a vaccine by the early 1960s. Influenza virus was detected for the first time in wild birds in 1961, which led to the identification of water fowl and shore birds as the natural reservoir of influenza A viruses. An apparent cross-species incursion of a feline parvovirus variant produced the worldwide epizootic of canine parvovirus in the late 1970s. Again, standard in-vitro cell culture procedures identified the new agent and soon enabled the production of an effective vaccine. The entire arterivirus family (Arteriviridae) was identified in the cell culture era of virologyāspecifically, equine arteritis virus (1953), lactate dehydrogenase-elevating virus (1960), simian hemorrhagic fever virus (1964), and porcine reproductive and respiratory syndrome virus (1991). The discovery of human immunodeficiency virus (HIV) in 1983 attracted global attention, but the identification of simian immunodeficiency virus shortly thereafter may ultimately be of equal importance to the eventual control of human HIV infection. The primate system provided the animal models for studies of pathogenesis and vaccine development, and the existence of the simian virus in Old World primates provided the link to the origin of HIV as a cross-species (species jumper) infection.
The beginnings of the molecular era of virology reside in the late 1970s and early 1980s. Although not related to virology, the development of the polymerase chain reaction (PCR) in 1983 was to have an impact on virology as has no other technique to date. Cloning of nucleic acid sequences led to the first infectious molecular clone of a virus (poliovirus) in 1981. The impact of molecular techniques on virus detection and diagnostics was demonstrated with the identification of hepatitis C virus by molecular means without isolation (in-vitro culture of the virus). Viruses that could not be easily cultured in vitroāsuch as papillomaviruses, noroviruses, rotaviruses, and certain nidovirusesācould now be characterized and routinely detected by tests at the molecular level. A remarkably impressive feat spear-headed by Jeffrey Taubenberger was the molecular reconstruction of an infectious virus from RNA fragments representing the pandemic 1918 influenza A virus. Dreams of recreating extinct animals by molecular techniques may be farfetched, but the possibility exists for determining the early precursors of currently circulating viruses. Rapid and inexpensive nucleotide sequencing strategies are again redefining virology, and whole genomic sequencing is likely to replace less exact procedures for identifying and characterizing virus isolates. Metagenomic analyses of water and soil samples have i...