Basic Virology. Martinez J. Hewlett

acquired immune deficiency syndrome(AIDS) epidemic, as well as sporadic occurrences of viral diseases such as hemorrhagic fevers in Asia, Africa, and the southwestern United States. Investigation of the course of a viral disease, as well as societal responses to it, provides a ready means to study the role of social policies and social behavior of disease in general.

      The recent worldwide spread of AIDS is an excellent example of the role played by economic factors and other aspects of human behavior in the origin of a disease. There is strong evidence to support the view that the causative agent, human immunodeficiency virus(HIV), was introduced into the human population by an event fostered by agricultural encroachment of animal habitats in Equatorial Africa. This is an example of how economic need has accentuated risk.

      HIV is not an efficient pathogen; it requires direct inoculation of infected blood or body fluids for spread. In the Euro‐American world, the urban concentration of homosexual males with sexual habits favoring a high risk for venereal disease had a major role in spreading HIV and resulting AIDS throughout the male homosexual community. A partial overlap of this population with intravenous drug users and participants in the commercial sex industry resulted in spread of the virus and disease to other portions of urban populations. The result is that in Western Europe and North America, AIDS has been a double‐edged sword threatening two disparate urban populations: the relatively affluent homosexual community and the impoverished heterosexual world of drug abusers – both highly concentrated urban populations. In the latter population, the use of commercial sex as a way of obtaining money resulted in further spread to other heterosexual communities, especially those of young, single men and women.

      An additional factor is that the relatively solid medical and financial resources of a large subset of the “economic first world” resulted in wide use of whole blood transfusion and, more significantly, pooled blood fractions for therapeutic use. This led to the sudden appearance of AIDS in hemophiliacs and sporadically in recipients of massive transfusions due to intensive surgery. Luckily, the incidence of disease in these last risk populations has been reduced owing to effective measures for screening blood products.

Different societal factors resulted in a different distribution of HIV and AIDS in Equatorial Africa and Southeast Asia. In these areas of the world, the disease is almost exclusively found in heterosexual populations. This distribution of AIDS occurred because a relatively small concentration of urban commercial sex workers acted as the source of infection of working men living apart from their families. The periodic travel by men to their isolated village homes resulted in the virus being found with increasing frequency in isolated family units. Further spread resulted from infected women leaving brothels and prostitution to return to their villages to take up family life.

      Another important factor in the spread of AIDS is technology. HIV could not have spread and posed the threat it now does in the world of a century ago. Generally lower population densities and lower concentrations of individuals at risk at that time would have precluded HIV from gaining a foothold in the population. Slower rates of communication and much more restricted travel and migration would have precluded rapid spread; also, the transmission of blood and blood products as therapeutic tools was unknown a century ago.

      Of course, this dynamic interaction between pathogen and host is not confined to viruses; any pathogen exhibits it. The study and characterization of the genetic accommodations that viruses make, both to natural resistance generated in a population of susceptible hosts and to human‐directed efforts at controlling the spread of viral disease, provide much insight into evolutionary processes and population dynamics. Indeed, many of the methodologies developed for the study of interactions between organisms and their environment can be applied to the interaction between pathogen and host.

The history of virology

      The historic reason for the discovery and characterization of viruses, and a continuing major reason for their detailed study, involve the desire to understand and control the diseases and attending degrees of economic and individual distress caused by them. As studies progressed, it became clear that there were many other important reasons for the study of viruses and their replication.

      Since viruses are parasitic on the molecular processes of gene expression and its regulation in the host cell, an understanding of viral genomes and virus replication provides basic information concerning cellular processes in general.

      The whole development of molecular biology and molecular genetics is largely based on the deliberate choice of some insightful pioneers of “pure” biological research to study the replication and genetics of viruses that replicate in bacteria: the bacteriophages. (Such researchers include Max Delbrück, Salvadore Luria, Joshua Lederberg, Gunther Stent, Seymour Benzer, André Lwoff, François Jacob, Jacques Monod, and many others.)

      The bacterial viruses (bacteriophages) were discovered through their ability to destroy human enteric bacteria such as Escherichia coli, but they had no clear relevance to human disease. It is only in retrospect that the grand unity of biological processes, from the simplest to the most complex, can be seen as mirrored in replication of viruses and the cells they infect.

      The biological insights offered by the study of viruses have led to important developments in biomedical technology and promise to lead to even more dramatic developments and tools. For example, when infecting an individual, viruses target specific tissues. The resulting specific signs and symptoms, as already noted, define their pathogenicity. The normal human, like all vertebrates, can mount a defined and profound response to virus infections. This response often leads to partial or complete immunity to reinfection. The study of these processes was instrumental to gaining an increasingly clear understanding of the immune response and the precise molecular nature of cell–cell signaling pathways. It also provided therapeutic and preventive strategies against specific virus‐caused disease. The study of virology has and will continue to provide strategies for the palliative treatment of metabolic and genetic diseases not only in humans, but also in other economically and aesthetically important animal and plant populations.

Examples of the impact of viral disease on human history

      There is archeological evidence in Egyptian mummies and medical texts of readily identifiable viral infections, including genital papillomas (warts) and poliomyelitis. There are also somewhat imperfect historical records of viral disease affecting human populations in classical and medieval times. While the recent campaign to eradicate smallpox has been successful and the virus no longer exists in the human population (owing to the effectiveness of vaccines against it, the genetic stability of the virus, and a well‐orchestrated political and social effort to carry out the eradication), the disease periodically wreaked havoc and had profound effects on human history over thousands of years. Smallpox epidemics during the Middle Ages and later in Europe resulted in significant population losses as well as major changes in the economic, religious, political, and social life of individuals. Although the effectiveness of vaccination strategies gradually led to decline of the disease in Europe and North America, smallpox continued to cause massive mortality and disruption in other parts of the world until after World War II. Despite smallpox being eradicated from the environment, the attack of September 11, 2001, on the World Trade Center in New York has led some government officials to be concerned that the high virulence of the virus and its mode of spread might make it an attractive agent for bioterrorism.

      Other virus‐mediated epidemics had equally major roles in human history. Much of the social, economic, and political chaos in native populations resulting from European conquests and expansion from the fifteenth through nineteenth centuries was mediated by introduction of infectious viral diseases such as measles. Significant fractions of the indigenous population of the Western Hemisphere died as a result of these diseases.

      Potential for major social and political disruption of everyday life continues to this day. As discussed in later chapters of this book, the “Spanish” influenza (H1N1)