Principles of Virology, Volume 2. S. Jane Flint

the Western Hemisphere Zoonotic Infections and Epidemics Caused by “New” Viruses The Economic Toll of Viral Epidemics in Livestock Population Density and World Travel Are Accelerators of Viral Transmission Focus on Frontline Health Care: Ebolavirus in Africa Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil

        Epidemiology Fundamental Concepts Methods Used by Epidemiologists Surveillance Network Theory and Practical Applications

        Parameters That Govern the Ability of a Virus to Infect a Population Geography and Population Density Climate

        Perspectives

        References

        Study Questions

      LINKS FOR CHAPTER 1

       Video: Interview with Dr. W. Thomas London http://bit.ly/Virology_London

       Epidemiology causes conclusions (p less than 0.01) http://bit.ly/Virology_Twiv169

       Slow motion sneezing http://bit.ly/Virology_1-23-13

       CD4 Hunter http://bit.ly/Virology_Twiv489

Swords, lances, arrows, machine guns, and even high explosives have had far less power over the fates of nations than the typhus louse, the plague flea, and the yellow-fever mosquito.

      HANS ZINSSER

      Rats, Lice and History, 1934

Introduction to Viral Pathogenesis

      While the title of Zinsser’s classic volume Rats, Lice and History may trigger a wry smile (for how, after all, could lice be part of history?), the ideas proposed in this famous history of pathogens and the diseases they cause remain as relevant today as when they were published in 1934. As Zinsser argued, the global impact of pathogens, including viruses, has shaped human history as much as any war, natural disaster, or invention. This view may seem an exaggeration to today’s student of virology, who may perceive most viral infections as annoyances that result in a few missed classes or days of work. But in the context of history, epidemics of smallpox, yellow fever, human immunodeficiency virus, and influenza have caused an incalculable loss of life and have changed entire societies. Smallpox alone killed well over 300 million people in the 20th century, more than twice the number of deaths from all the wars that occurred in the same time period. Huge empires fell to a relatively small number of invaders, in part because the conquerors inadvertently introduced viruses that crippled the empires’ defense forces. Not all such victories were accidental, however: in the 1760s, British traders offered blankets and handkerchiefs from the smallpox hospital at Fort Pitt to American Indians who had never been exposed to this pathogen. As William Trent, one of the traders, noted, “I hope it will have the desired effect.” Smallpox, used in this way, was the first bioweapon.

      Although vaccines and antivirals have reduced, and even eliminated, some of these scourges, we are reminded of the challenges we still face by the looming threat of an influenza pandemic, the devastation caused by Ebolaviruses in Africa, the lack of success in developing a human immunodeficiency virus vaccine, and the resurgence of vaccine-preventable infections. We also face the emergence of “new” human viral pathogens, such as the coronavirus that is the cause of the worldwide pandemic in 2019–2020, and Zika virus, which causes gross defects in brain formation. Of equal importance, viruses that cause disease in crops and animals have crippling consequences for the infected species, the farmers who depend on them for their livelihoods, and human populations that may face starvation.

      The ways that viruses cause diseases in their hosts, the tug-of-war among viruses and the host’s defenses, and the impact that viral epidemics have had on human, animal, and plant populations are therefore not just interesting academic pursuits, but rather life-and-death issues for all organisms. That said, it is important to bear in mind this critical principle: pathogenesis (the processes that lead to disease) is often a collateral outcome of the parasitic nature of viruses. As is true for humans, selective pressures that control evolution of viruses act only on their abilities to survive and reproduce. From this perspective, one could argue that the most successful viruses are those that cause no apparent disease in their natural host.

      In the first chapter of Volume I, we recounted an abbreviated history of virology and described milestones that established the foundation for our current understanding of viral reproduction. In this chapter, we return to history, focusing on watershed events that catalyzed the fields of viral epidemiology and pathogenesis. Subsequent chapters in this volume will consider the impact of viral infections on individual hosts, tissues, and cells. Our goal in Volume II is to build on the principles of viral reproduction that were established in Volume I, providing an integrated view of how viruses cause disease in single cells, discrete hosts, and large populations, as well as the host responses that mitigate or prevent such diseases.

      PRINCIPLES Introduction to viral pathogenesis

       Diseases associated with viral infections are a collateral outcome of the parasitic nature of these pathogens.

       Koch’s postulates helped to identify causal relationships between a microbe and the disease it causes in the host, although these postulates may not be fulfilled when associating some viruses with a particular disease.

       Major insights in viral pathogenesis have come from exploitation of technical advances in the fields of molecular biology and immunology.

       The increased mobility of human and animal populations on the planet has accelerated the emergence of epidemics.

       Many viruses that can infect multiple species establish a reservoir in an animal host in which the virus causes negligible disease. Spread into new human hosts, called a zoonosis, is usually a dead-end infection.

       Epidemiology, the study of infections in populations, is the cornerstone of public health research and response.

       Individual differences among prospective hosts, group dynamics and behaviors, geography, and climate all influence how efficiently a virus can establish infection within a population.

       The regional occurrence of viral infections may be due to the restriction of a vector or animal reservoir to a limited geographical area.

       Seasonal