Why We Need To Study Viruses.Viruses Are Everywhere Viruses are all around us, comprising an enormous proportion of our environment, in both number and total mass (Box 1.1). All living things encounter billions of virus particles every day. For example, they enter our lungs in the 6 liters of air each of us inhales every minute; they enter our digestive systems with the food we eat; and they are transferred to our eyes, mouths, and other points of entry from the surfaces we touch and the people with whom we interact. Our bodies are reservoirs for viruses that reside in our respiratory, gastrointestinal, and urogenital tracts. In addition to viruses that can infect us, our intestinal tracts are loaded with myriad plant and insect viruses, as well as hundreds of bacterial species that harbor their own constellations of viruses.
Viruses Can Cause Human Disease.
With such constant exposure, it is nothing short of amazing that the vast majority of viruses that infect us have little or no impact on our health or well-being. As described in Volume II, we owe such relative safety to our elaborate immune defense systems, which have evolved to fight microbial infection. When these defenses are compromised, even the most common infection can be lethal. Despite such defenses, some of the most devastating human diseases have been or still are caused by viruses; these diseases include smallpox, yellow fever, poliomyelitis, influenza, measles, and AIDS. Viral infections can lead to life-threatening diseases that impact virtually all organs, including the lungs, liver, central nervous system, and intestines. Viruses are responsible for approximately 20% of the human cancer burden, and viral infections of the respiratory and gastrointestinal tracts kill millions of children in the developing world each year. As summarized in Volume II, Appendix, there is no question about the biomedical importance of these agents.
Viruses Infect All Living Things While most of this textbook focuses on viral infections of humans, it is important to bear in mind that viruses also infect pets, food animals, plants, insects, and wildlife throughout the world. They infect microbes such as algae, fungi, and bacteria, and some even interfere with the reproduction of other viruses. Viral infection of agricultural plants and animals can have enormous economic and societal impact. Outbreaks of infection by foot-and-mouth disease and avian influenza viruses have led to the destruction (culling) of millions of cattle, sheep, and poultry to prevent further spread. Losses in the United Kingdom during the 2001 outbreak of foot-andmouth disease ran into billions of dollars and caused havoc for both farmers and the government (Box 1.2). More recent outbreaks of the avian influenza virus H5N1 in Asia have resulted in similar disruption and economic loss. Viruses that infect crops such as potatoes and fruit trees are common and can lead to serious food shortages as well as financial devastation.
Viruses Can Be Benefcial.
Despite the appalling statistics from human and agricultural epidemics, it is important to realize that viruses can also be beneficial. Such benefit can be seen most clearly in marine ecology, where virus particles are the most abundant biological entities (Box 1.1). Indeed, they comprise 94% of all nucleic acid-containing particles in the oceans and are 15 times more abundant than the Bacteria and Archaea. Viral infections in the ocean kill 20 to 40% of marine microbes daily, converting these living organisms into particulate matter, and in so doing release essential nutrients that supply phytoplankton at the bottom of the ocean’s food chain, as well as carbon dioxide and other gases that affect the climate of the earth. Pathogens can also influence one another: infection by one virus can have an ameliorating effect on the pathogenesis of a second virus or even bacteria. For example, human immunodeficiency virus-infected AIDS patients show a substantial decrease in their disease progression if they are persistently infected with hepatitis G virus, and mice latently infected with some murine herpesviruses are resistant to infection with the bacterial pathogens Listeria monocytogenes and Yersinia pestis. The idea that viruses are solely agents of disease is giving way to the notion that they can exert positive, even necessary, effects.
Viruses Can Cross Species Boundaries
Although viruses generally have a limited host range, they can and do spread across species barriers. As the world’s human population continues to expand and impinge on the wilderness, cross-species (zoonotic) infections of humans are occurring with increasing frequency. In addition to the AIDS pandemic, the highly fatal Ebola hemorrhagic fever and the severe acute respiratory syndrome (SARS) are recent examples of viral diseases to emerge from zoonotic infections. The current pandemic of influenza virus H5N1 in avian species has much of the world riveted by the frightening possibility that a new, highly pathogenic strain might emerge following transmission from birds to human hosts. Indeed, given the eons over which viruses have had the opportunity to interact with various species, today’s “natural” host may simply be a way station in viral evolution.
Viruses “R” Us Every cell in our body contains viral DNA. Human endogenous retroviruses, and elements thereof, make up about 5 to 8% of our DNA. Most are inactive, fossil remnants from infections of germ cells that have occurred over millions of years during our evolution. Some of them are suspected to be associated with specific diseases, but the protein products of other endogenous retroviruses are essential for placental development.
Viruses Are Unique Tools To Study Biology Because viruses are dependent on their hosts for propagation, studies that focus on viral reprogramming of cellular mechanisms have provided unique insights into cellular biology and functioning of host defenses. Groundbreaking studies of viruses that infect bacteria, the bacteriophages, laid the foundations of modern molecular biology (Table 1.1), and crystallization of the plant virus tobacco mosaic virus was a landmark in structural biology. Studies of animal viruses established many fundamental principles of cellular function, including the presence of intervening sequences in eukaryotic genes. The study of cancer (transforming) viruses revealed the genetic basis of this disease. It seems clear that studies of viruses will continue to open up such paths of discovery in the future. With the development of recombinant DNA technology and our increased understanding of some viral systems, it has become possible to use viral genomes as vehicles for the delivery of genes to cells and organisms for both scientific and therapeutic purposes. Te use of viral vectors to introduce genes into various cells and organisms to study their function has become a standard method in biology.
Virus Prehistory Although viruses have been known as distinct biological entities for little more than 100 years, evidence of viral infection can be found among the earliest recordings of human activity, and methods for combating viral disease were practiced long before the first virus was recognized. Consequently, efforts to understand and control these important agents of disease are phenomena of the 20th century.