Viruses Prions and Viroids Infectious Agents of Animals and Plants

Transmission electron micrograph (TEM) of rotavirus (x575,000)

/ | Ithough scientific reports as early as the eighteenth century suggested that invisible agents might cause * * tumors, not until the early twentieth century did this idea gain strong experimental support. At that time, Dr. Peyton Rous of the Rockefeller Institute caused tumors in healthy chickens by injecting them with a filtered suspension of ground-up cells from tumors of other chickens. These studies were not taken very seriously, because most people believed that viruses did not cause tumors. As years passed, however, the idea gained favor as other investigators made similar observations. For example, in the early 1930s, Dr. Richard Shope observed skin tumors (papillomas) in wild rabbits in Iowa and Kansas. He showed that these tumors were caused by an agent that was not trapped in filters that removed bacteria. When he injected the filtrate into domestic rather than wild rabbits, the agent did not cause tumors. This phenomenon of a virus causing a disease in one animal but not in another has since been observed again and again with many other viruses.

In 1957, almost 50 years after Peyton Rous's study, Dr. Sarah Stewart and Dr. Bernice Eddy at the National Institutes of Health in Washington, D.C., studied two tumor-causing viruses, polyoma, a DNA virus, and SV40, an RNA virus. They noted that when the polyoma virus, grown in monkeys or mouse embryo tissues, was inoculated into a wide variety of animals such as rats, hamsters, and rabbits, it caused many different kinds of tumors. Eddy also pioneered the study of SV40, a virus that could be isolated from certain monkeys in which it did not cause any tumors. When injected into other animals, such as baby hamsters, however, the virus caused tumors. Thus, SV40, like the papilloma virus studied by Shope, appears to be "silent" in its natural host but causes tumors when inoculated into certain foreign hosts.

Recently, the ability of SV40 to cause tumors in hamsters has taken on a new twist. Early batches of the injectable polio vaccine prepared by Dr. Jonas Salk in 1955 were derived from healthy rhesus monkeys that were contaminated with SV40. Several hundred million people worldwide were injected with the contaminated vaccine before virus-free preparations of the vaccine were manufactured, starting in 1961. Until the early 1990s, there was no indication that children who were given the contaminated vaccine were in any danger of developing tumors from the SV40. However, in 1992, SV40 DNA was found in rare childhood brain tumors and then in bone tumors. These findings were followed by finding SV40 DNA in lung tumors and, in 2002, the virus was found in non-Hodgkin's lymphoma. Not all of the people who had SV40 in their tumors had been inoculated with the contaminated polio vaccine. It seems likely that the virus spread from people who were given the contaminated vaccine to those who were not. However, finding SV40 in human tumors does not prove that the virus caused the tumor. Indeed, several studies have concluded that people who received the contaminated vaccine do not have an increased risk of developing tumors. More research is needed to understand the true significance of finding SV40 in so many different types of tumors. Such research is in progress.

—A Glimpse of History

MUCH OF THE BASIC BIOLOGY OF BACTERIOPHAGES also applies to animal and plant viruses; however, each viral group has certain unique properties. This chapter presents a general approach to the classification of animal viruses, followed by a discussion of their modes of replication and effects on host cells, including their role in causing certain tumors. A discussion of plant viruses as well as viroids and prions is also included.

342 Chapter 14 Viruses, Prions, and Viroids: Infectious Agents of Animals and Plants

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