Viruses Cause Disease But Are Also Useful as Tools

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Viruses are of intense interest because many cause serious illness in humans or domestic animals, and others damage crop plants. During the last century, progress in the control of infectious diseases through improved sanitation, safer water supplies, the development of antibiotics and vaccines, and better medical care have dramatically reduced the threat to human health from these agents, especially in developed countries. This is illustrated in Fig. 1.1, in which the death rate from infectious disease in the United States during the last century is shown. At the beginning of the 20th century, 0.8% of the population died each year from infectious diseases. Today the rate is less than one-tenth as great. The use of vaccines has led to effective control of the most dangerous of the viruses. Smallpox virus has been eradicated worldwide by means of an ambitious and concerted effort, sponsored by the World Health Organization, to vaccinate all people at risk for the disease. Poliovirus has been eliminated from the Americas, and measles virus eliminated from North America, by intensive vaccination programs. There is hope that these two viruses can also be eradicated worldwide in the near future. Vaccines exist for the control of many other viral diseases, such as mumps, rabies, rubella, yellow fever, and Japanese encephalitis.

The dramatic decline in the death rate from infectious disease has led to a certain amount of complacency. There is a small but vocal movement in the United States to eliminate immunization against viruses, for example. However,

1900 1920 1940 1960 1980 2000

1900 1920 1940 1960 1980 2000

Year

FIGURE 1.1 Death rate from infectious disease in the United States, 1900-1996. The death rate has dropped over this century from around 800 deaths per 100,000 population per year to about 50. Significant milestones in public health are shown. After dropping steadily for 80 years, interrupted only by the influenza pandemic of 1918-1919, the death rate began to rise in 1980 with the advent of the AIDS epidemic. From Morbidity and Mortality Weekly Report (MMWR), Vol. 48, No. 29, p. 621 (1999).

viral diseases continue to plague humans, as do infectious diseases caused by bacteria, protozoa, fungi, and multicel-lular parasites. Deaths worldwide due to infectious disease are shown in Fig. 1.2, divided into six categories. In 1998 more than 3 million deaths occurred as a result of acute respiratory disease, many of which are caused by viruses. More than 2 million deaths were attributed to diarrheal diseases, about half of which are due to viruses. AIDS killed 2 million people worldwide in 1998, and measles is still a significant killer in developing countries. Recognition is growing that infectious diseases, of which viruses form a major component, have not been conquered by the introduction of vaccines and drugs. The overuse of antibiotics has resulted in an upsurge in antibiotic-resistant bacteria, and viral diseases continue to resist elimination.

The persistence of viruses is in part due to their ability to change rapidly and adapt to new situations. Human immunodeficiency virus (HIV) is the most striking example of the appearance of a virus that has recently entered the human population and caused a plague of worldwide importance. The arrival of this virus in the United States caused a significant rise in the number of deaths from infectious disease, as seen in Fig. 1.1. Other, previously unde-scribed viruses also continue to emerge as serious pathogens. Sin Nombre virus caused a 1994 outbreak in the United States of hantavirus pulmonary syndrome with a

50% case fatality rate, and it is now recognized as being widespread in North America. Junin virus, which causes Argentine hemorrhagic fever, and related viruses have become a more serious problem in South America with the spread of farming. Ebola virus, responsible for several small African epidemics with a case fatality rate of 70%, was first described in the 1970s. Nipah virus, previously unknown, appeared in 1998 and caused 258 cases of encephalitis, with a 40% fatality rate, in Malaysia and Singapore. As faster and more extensive travel becomes ever more routine, the potential for rapid spread of all viruses increases. The possibility exists that any of these viruses could become more widespread, as has HIV since its appearance in Africa perhaps half a century ago, and as has West Nile virus, which spread to the Americas in 1999.

Newly emerging viruses are not the only ones to plague humans, however. Many viruses that have been known for a long time, and for which vaccines may exist, continue to cause widespread problems. Respiratory syncytial virus, as an example, is a major cause of pneumonia in infants. Despite much effort, it has not yet been possible to develop an effective vaccine. Even when vaccines exist, problems may continue. For example, influenza virus changes rapidly and the vaccine for it must be reformulated yearly. Because the major reservoir for influenza is birds, it is not possible to eradicate the virus. Thus, to control influenza would

Disease

Disease

Millions of Deaths per Year

FIGURE 1.2 Six leading infectious diseases as causes of death. Data are the totals for all ages worldwide in 1995 and in 1998. The data came from the World Health Organization web site: http://www:who.int/infectious-disease-report/pages/graph5.html.

Millions of Deaths per Year

FIGURE 1.2 Six leading infectious diseases as causes of death. Data are the totals for all ages worldwide in 1995 and in 1998. The data came from the World Health Organization web site: http://www:who.int/infectious-disease-report/pages/graph5.html.

require that the entire population be immunized yearly. This is a formidable problem and the virus continues to cause annual epidemics with a significant death rate (Chapter 4). Although primarily a killer of the elderly, the potential of influenza to kill the young and healthy was shown by the worldwide epidemic of influenza in 1918 in which 20-100 million people died worldwide. In the United States, perhaps 1% of the population died during the epidemic (Fig. 1.1). Continuing study of virus replication and virus interactions with their hosts, surveillance of viruses in the field, and efforts to develop new vaccines as well as other methods of control are still important.

The other side of the coin is that viruses have been useful to us as tools for the study of molecular and cellular biology. Further, the development of viruses as vectors for the expression of foreign genes has given them a new and expanded role in science and medicine, including their potential use in gene therapy (Chapter 9). As testimony to the importance of viruses in the study of biology, numerous Nobel Prizes have been awarded in recognition of important advances in biological science that resulted from studies that involved viruses (Table 1.1). To cite a few examples, Max Delbrück received the prize for pioneering studies in what is now called molecular biology, using bacteriophage T4. Cellular oncogenes were first discovered from their presence in retroviruses that could transform cells in culture, a discovery that resulted in a prize for Francis Peyton Rous for his discovery of transforming retroviruses, and for Michael Bishop and Harold Varmus, who were the first to show that a transforming retroviral gene had a cellular counterpart. As a third example, the development of the modern methods of gene cloning have relied heavily on the use of restriction enzymes and recombinant DNA technology, first developed by Daniel Nathans and Paul Berg working with SV40 virus, and on the use of reverse tran-scriptase, discovered by David Baltimore and Howard Temin in retroviruses. As another example, the study of the interactions of viruses with the immune system has told us much about how this essential means of defense against disease functions, and this resulted in a prize for Rolf Zinkernagel and Peter Doherty. The study of viruses and their use as tools has told us as much about human biology as it has told us about the viruses themselves.

In addition to the interest in viruses that arises from their medical and scientific importance, viruses form a fascinating evolutionary system. There is debate as to how ancient are viruses. Some argue that RNA viruses contain remnants of the RNA world that existed before the invention of DNA. All would accept the idea that viruses have been present for hundreds of millions of years and have helped to shape the

TABLE 1.1 Nobel Prizes Involving Virology3

Year

Names

Nobel citation; virus group or family

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