Prions are a group of noncellular infectious agents that are not vi ruses and really belong in a category all by themselves. The term prion is derived from the words proteinaceous infectious particle to suggest its primary structure: a naked protein molecule. They are the only biologically active agent that lacks any sort of nucleic acid (DNA or RNA) and were unknown until the early 1980s.
The diseases associated with prions are known as transmissible spongiform encephalopathies (TSEs). This description recognizes that the diseases are spread from host to host by direct contact, contaminated food, or other means. It also refers to the effects of the agent on nervous tissue, which develops a spongelike appearance due to loss of nerve and glial cells. Another pathological effect observed in these diseases is the buildup of tiny protein fibrils in the brain tissue (process figures 1a and 1b). Several forms of prion diseases are known in mammals, including scrapie in sheep; bovine spongiform encephalopathy (mad cow disease) in cattle; and wasting disease in elk, deer, and mink. These diseases have a long latent period (usually several years) before the first symptoms of brain degeneration appear. The animals lose coordination, have difficulty moving, and eventually collapse and die.
Fig1. The appearance and mechanism of prion-based diseases. (a) A magnified view of nerve cells infected with prion protein. Red areas indicate places in the cytoplasm where the prion fibers have deposited. (b) A diagram of a nerve cell to outline the stages in the conversion of normal prions (PrPC) into diseased prions (PrPSc) and the formation of prion fibers. (a): National Institute of Allergy and Infectious Diseases
Humans are host to similar chronic diseases, including Creutzfeldt-Jakob disease (CJD), kuru, and fatal familial insomnia. In all of these conditions, the brain progressively deteriorates and the patient loses coordination, along with sensory and cognitive abilities. There is no treatment, and most cases so far have been fatal. In the 1990s, a different form of CJD—known as variant CJD or vCJD—was identified. One of the primary differences between the two forms of the disease is that the median age of death for patients with CJD is 68, while for those with vCJD, it is 28. The dis ease was traced to people eating meat from cows infected with the bovine form of encephalopathy. The cows were believed to have become infected by eating the nervous tissue of infected sheep. The sheep tissue, known as offal, was ground and added to cattle feed as a source of protein. Several hundred people developed the disease (nearly all in Western Europe and Saudi Arabia), and most of them have since died. This was the first indicator that prions of animals could cause infections in humans. It sparked a crisis in the beef industry and strict controls on imported beef. Although only three cases of human disease have occurred in the United States, infected cattle have been reported.
Researchers discovered that normal prion proteins (abbreviated PrPC) are commonly found on the membrane of cells. When the infectious form of the prion (abbreviated PrPSc, with the Sc referring to scrapies) encounters a normal PrPC protein, it can induce spontaneous abnormal folding in the normal protein, converting it to PrPSc. Ultimately, the buildup of these converted proteins dam ages and kills the cell (process figure 1b). Another serious issue with prions is their extreme resistance. They are not destroyed by disinfectants, radiation, or the usual sterilization techniques. Even treatments with extreme high temperatures and concentrated chemicals are not always reliable methods to eliminate them.
Other fascinating viruslike agents in human disease are defective forms called satellite viruses that depend on other viruses for replication. Two remarkable examples are the adeno-associated virus (AAV), which can replicate only in cells infected with adenovirus, and the delta agent, a naked strand of RNA that is expressed only in the presence of the hepatitis B virus and can worsen the severity of liver damage.
Plants may be parasitized by viruslike agents called viroids that differ from ordinary viruses by being very small (about one-tenth the size of an average virus) and being composed of only naked strands of RNA, lacking a capsid or any other type of coating. The existence of these unusual agents is one bit of supportive evidence that viruses may have evolved from naked bits of nucleic acid. Viroids are significant pathogens in several economically important plants, including tomatoes, potatoes, cucumbers, citrus trees, and chrysanthemums.
