Basic Virology. Martinez J. Hewlett

spread due to its lack of persistence and its engendering of a strong and lasting immunity. Since related poxviruses are found in many animals maintaining large populations, introduction into humans after the development of agriculture and urbanization can be inferred. The same can be said for polio, measles, Ebola, and other viral diseases, which spread by acute infection and leave an immune population cleared of virus in their path. Indeed, Jared Diamond has made a strong case for such diseases being a critical feature in the development of modern, urban society in his book Guns, Germs, and Steel: The Fates of Human Societies.

PATTERNS OF SPECIFIC VIRAL DISEASES OF HUMANS

      While classification of human viruses according to the history of their association with us as host is very useful from an epidemiological and evolutionary point of view, a classification of these viruses by the nature of the disease they cause and its sequelae is more useful from a medical perspective. Some important viral diseases are classified in this way throughout this section.

Acute infections followed by virus clearing

       Colds and respiratory infections

      Cold viruses (rhinoviruses, adenoviruses, and coronaviruses) are spread as aerosols. Infection is localized within the nasopharynx, and recovery involves immunity against that specific virus serotype. The vast array of different cold viruses and serotypes ensures that there will always be another one to infect individuals. Although generally these types of respiratory diseases are mild, infection of an immune‐compromised host or a person having complications due to another disease or advanced age can lead to major problems.

Influenza

      The epidemiology of influenza is an excellent model for the study of virus spread within a population. While symptoms can be severe, in part due to host factors, the virus infection is localized, and the virus is efficiently cleared from the host. Flu viruses have evolved unique mechanisms to ensure constant generation of genetic variants, and the constant appearance of new influenza virus serotypes leads to periodic epidemics of the disease. Some of these mechanisms are described in detail in Chapter 15, Part IV. The respiratory distress caused by most strains of flu virus is not particularly life‐threatening for healthy individuals, but poses a serious problem for older people and individuals with immune system or respiratory deficiencies. Some strains of the virus cause more severe symptoms with accompanying complications than others. At least one strain, the Spanish strain of 1918–1919 (H1N1), caused a worldwide epidemic with extremely high mortality rates in the years immediately following World War I.

Variola

The disease caused by infection with smallpox (variola) virus is an example of a much more severe disease than flu, with correspondingly higher mortality rates. There are (or were) two forms of the disease: variola major and variola minor. These differed in severity of symptoms and death rates. Death rates for variola major approached 20%, and during the Middle Ages in Europe, it reached levels of 80% or higher in isolated communities. Virus spread was generally by inhalation of virus aerosols formed by drying exudate from infected individuals. Variola virus is unusually resistant to inactivation by desiccation, and examples of transmission from contaminated material as long as several years after active infection were common.

      The disease involves dissemination of virus throughout the host and infection of the skin. Indeed, the pathogenesis of mouse pox described in Chapter 3 provides a fairly accurate model of smallpox pathogenesis. The virus encodes growth factors that were originally derived from cellular genes. These growth factors induce localized proliferation at sites of infection in the skin, which results in development of the characteristic pox (see Chapter 18, Part IV).

Infection of an “accidental” target tissue leading to permanent damage despite efficient clearing

As outlined in Figure 4.2, some viruses can target and damage an organ or organ system in such a way that recovery from infection does not lead to the infected individual regaining full health despite generation of good immunity. A well‐understood example is paralytic poliomyelitis. Poliovirus is a small enteric virus with an RNA genome (a picornavirus), and most infections (caused by ingestion of fecal contamination from an infected individual) are localized to the small intestine. Infections are often asymptomatic, but can lead to mild enteritis and diarrhea. The virus is introduced into the immune system by interaction with lymphatic tissue in the gut, and an effective immune response is mounted, leading to protection against reinfection.

      Infection with poliovirus, however, can also lead to paralytic polio. The cellular surface protein to which the virus must bind for cellular entry (CD155) is found only on cells of the small intestine and on motor neurons. In rare instances, infection with a specific genotype that displays marked tropism for (a propensity to infect) neurons (i.e., a neurovirulent strain) leads to a situation where virus infects motor neurons and destroys them. In such a situation, destruction of the neurons leads to paralysis.

      It should be noted that paralysis resulting from neuronal infection does not aid the virus's spread among individuals; this paralytic outcome is a “dead end.” Perhaps ironically, the paralytic complications of poliovirus infections have had negative selective advantages, since if such a dramatic outcome did not occur, there would have been no interest in developing a vaccine against poliovirus infection!

      A variation on the theme of accidental destruction of neuronal targets by an otherwise relatively benign course of acute virus infection can be seen in rubella. This disease (also called German measles), which is caused by an RNA virus, is a mild (often asymptomatic) infection resulting in a slight rash. Although infection is mild in an immunocompetent individual, the virus has a strong tropism for replicating and differentiating neural tissue. Therefore, women in the first trimester of pregnancy who are infected with rubella have a very high probability of having an infant with severe neurological damage from congenital rubella syndrome. Rubella is rare in the United States due to high acceptance of the vaccine, but vaccination of women who are planning to become pregnant is an effective method of preventing such damage during localized rubella epidemics in other parts of the world.

Persistent viral infections

While persistent viral infections often indicate a long history of coevolution between virus and host, the lack of serious consequences to the vast majority of those infected does not mean that debilitating or lethal consequences are not possible. This is especially the case in situations where the immune system of the infected individual is compromised or has not yet developed. Some examples of persistent infections and the complications that can arise from these infections are shown in Figure 4.2.

Figure 4.2 Examples of virus infection of specific organs or organ systems. (a) DNA genome viruses. (b) RNA genome viruses. Blue labels indicate acute infections, while pink labels indicate infections that result in either chronic disease states or carcinomas. Red labels indicate acute infections that can result in severe disease.