Principles of Virology. Jane Flint

of viruses that can be present in or on a normal human (including some potential pathogens) has increased greatly with the development of high-throughput sequencing techniques and new bioinformatic tools. Current estimates of the numbers of distinct viral families with DNA or RNA genomes in various sites are in parentheses; the > symbol signifies the presence of additional viruses not yet assigned to known families. The numbers may increase as diagnostic tools improve and new viral families are identified. Data from Popgeorgiev N et al. 2013. Intervirology 56:395-412; see also http://www.virology.ws/2017/03/23/the-viruses-in-your-blood/.

BOX 1.2

      DISCUSSION

       The first animal virus discovered remains a scourge today

      Foot-and-mouth disease virus infects domestic cattle, pigs, and sheep, as well as many species of wild animals. Although mortality is low, morbidity (illness) is high and infected farm animals lose their commercial value. The virus is highly contagious, and the most common and effective method of control is by the slaughter of entire herds in affected areas.

      Outbreaks of foot-and-mouth disease were widely reported in Europe, Asia, Africa, and South and North America in the 1800s. The largest epidemic ever recorded in the United States occurred in 1914. After entry into the Chicago stockyards, the virus spread to more than 3,500 herds in 22 states. This calamity accelerated epidemiological and disease control programs, eventually leading to the field- and laboratory-based systems maintained by the U.S. Department of Agriculture to protect domestic livestock from foreign animal and plant diseases. Similar control systems have been established in other Western countries, but this virus still presents a formidable challenge throughout the world. A 1997 outbreak of foot-and-mouth disease among pigs in Taiwan resulted in economic losses of greater than $10 billion.

      In 2001, an epidemic outbreak in the United Kingdom spread to other countries in Europe and led to the slaughter of more than 6 million infected and uninfected farm animals. The associated economic, societal, and political costs jolted the British government. Images of mass graves and horrific pyres consuming the corpses of dead animals (see figure) sensitized the public as never before. Minor outbreaks that occurred later in the United Kingdom and parts of Asia were also controlled by culling. But in 2011, South Korea was reported to have destroyed 1.5 million pigs, roughly 12% of its population, to curb a more serious outbreak spread of the virus.

       Hunt J.3 January 2013. Foot-and-mouth is knocking on Europe’s door. Farmers Weekly. https://www.fwi.co.uk/livestock/health-welfare/livestock-diseases/livestock-foot-mouth/foot-and-mouth-is-knocking-on-europe-s-door.

       Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ. 1999. Veterinary Virology, 3rd ed. Academic Press, Inc, San Diego, CA.

      Mass burning of cattle carcasses during the 2001 foot-and-mouth disease outbreak in the United Kingdom. Courtesy of Dr. Pamela Hullinger, California Department of Food and Agriculture.

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 under the selective pressure imposed by 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 15% 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 Can Be Beneficial

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 the marine ecosystem, 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 Bacteria and Archaea. Viral infections in the ocean kill 20 to 40% of marine microbes daily, converting these living organisms into particulate matter. In so doing they 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, 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 an appreciation of their positive, even necessary, effects, and a realization that their unique properties can actually be harnessed for human benefit (Volume II, Chapter 9).

Viruses “R” Us

      Every cell in our body contains viral DNA. Human endogenous retroviruses, and elements thereof, make up about 8% of our genome. Most are inactive, fossil remnants from infections of germ cells that occurred over millions of years during our evolution. Some of them are suspected to be associated with specific diseases, but the regulatory sequences and protein products of other endogenous retroviruses have been coopted during our evolution for their unique functions. For example, retroviral gene products may play a role in the regulation of pluripotency in germ cells, in transmission of signals at neuronal synapses, and clearly in the way that we give birth. The development of the human placenta depends on cell fusion promoted by a retroviral protein. If not for these endogenous retroviruses, we might be producing our young in eggs, like birds and reptiles.

      Recent genomic studies have revealed that our viral “heritage” is not limited to retroviruses. Human and other vertebrate genomes harbor sequences derived from several other RNA and DNA viruses. As many of these insertions are estimated to have occurred some 40 million to 90 million years ago, this knowledge has provided unique insight into the ages and evolution of their currently circulating relatives. The conservation of some of these viral sequences in vertebrate genomes suggests that they may have been selected for beneficial properties over evolutionary time.

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, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) are recent examples of viral diseases to emerge from zoonotic infections. The influenza virus H5N1 continues to spread among poultry and wild birds in areas of the Middle East and Asia. The virus is deadly to