SECT ION I Introduction: RNA viruses

Viruses that infect the central nervous system may cause acute, chronic, or latent infections. In some cases, the diseases manifested are attributable to viral damage of neurons or supporting parenchymal tissues; in other cases, to immune attack on virally infected cells. They can be spread by excretion, by respiratory droplets or fomites, or, alternatively, by bites of insects or animals. These viruses range from those such as polio (Chapter 1) or rabies (Chapter 3), whose history in man is as old as the earliest records, to those that emerge from animal reservoirs to human hosts for the first time, such as SARS, Hendra, and Nipah viruses (see Chapter 21). In this section of Neurotropic virus infections, viruses with an RNA genome are described, starting with the simplest, picornaviruses (Chapter 1), to the most complex, alphaviruses (Chapter 6) and flaviviruses (Chapter 7). RNA viruses require an enzyme not found in host cells: RNA-dependent RNA polymerases to generate both sense (mRNA) and antisense RNA copies. Because of the lack of the host cell proofreading capacity for genome copying, errors are frequently introduced. Some of these errors are neutral, others may be deleterious (and are selected against) or, alternatively, potentially beneficial in evading host immune responses ranging from innate immune recognition to host adaptive immune recognition by Th1 or CD8 cells of epitopes expressed by host MHC or MHC molecules, respectively, or of antibody recognition of native proteins expressed by virions or infected host cells. These chapters are designed to describe the viruses, the diseases they cause, the epidemiology and transmission,medical treatment, as well as outline the areas for future advances. Neurotropic picornaviruses (Chapter 1) are important pathogens causing gastroenteritis and then acute paralytic diseases. Polioviruses were virtually extinguished from human populations (their only hosts) by the efficacy of the Salk and Sabin vaccines. But poliomyelitis is nowundergoing a re-emergence due to issues of religion, politics, and third-world sanitary deficiencies. Measles virus (Chapter 2) normally causes an acute respiratory and then systemic infection accompanied by a characteristic rash; the attenuated live virus vaccine for this disease is highly effective. However, in a few people who develop natural infections, a chronic infection develops in the central nervous system (CNS), which is identified by its accompanying pathology: subacute sclerosing panencephalitis (SSPE). Unlike the last two infections, which are spread from person to person, rabies is transmitted by the bite of a rabid animal or bat (see Chapter 21) and replicates locally before crossing the neuromuscular junction and entering peripheral nerves (Chapter 3). Retrograde transport brings the virus to theCNS,where thecharacteristicdisease ismanifest. It is among a growing group of viruses that have survived due to the development of proteins that block host responses. Like measles, coronaviruses are spread by the respiratory route (Chapter 4). While most human