All of the viruses in the four families of human pathogens classified in this group contain helical nucleocapsids within an enveloped particle. There are three general factors that govern gene expression in these viruses. First, the viral polymerase initiates transcription only at one end of the viral genome and reinitiates with approximately 50% efficiency following termination at the end of each gene. This property makes gene order an important means by which the relative levels of proteins are regulated. Second, the decision by the polymerase whether to transcribe mRNAs or replicate the entire genome is determined by the relative levels of the viral nucleocapsid protein. If levels are sufficient to package the nascent transcript, the polymerase ignores termination signals and proceeds copying the RNA template. Finally, cotranscriptional editing—the insertion of additional uncoded nucleotides by the viral poly-merase—occurs at a select homopolymer run in all paramyxovirus genomes. This property is probably related to the tendency of the polymerase to stutter on poly(U) stretches to generate the poly(A) tail. In addition to the natural human viruses outlined below, it should also be noted that the technology to create recombinant negative-sense viruses has been developed.
The four families of negative-sense, single-stranded RNA viruses contain several classical and emerging human viruses of notoriety. The first family, the Paramyxoviridae, contains four major human viruses that all initiate infection in the upper respiratory tract. Measles and mumps viruses cause once-common childhood maladies (fever/rash and parotitis syndromes, respectively) that are preventable by live attenuated vaccines given as part of the MMR series. The four serotypes of human parainfluenza virus are responsible for numerous seasonal respiratory infections in children, most notably croup. The last member of the paramyxoviruses, respiratory syncytial virus, is the number one respiratory pathogen for children in terms of disease severity. No vaccine is currently available to prevent infection by the last two members of the paramyxoviruses. Prophylactic doses of anti-RSV IgG is currently being given to reduce to the risk of respiratory syncytial virus infection in highly susceptible groups of children. The major member of the next family, the Rhab-doviridae, is rabies virus. This bullet-shaped virion is usually acquired through the bite of a rabid animal (most notably bats in recent years). Following replication at the site of infection, the virus travels to the CNS, where it invariably results in death. Because of the protracted time it takes for the virus to cross the neuromuscular junction to infect the nervous system, this is the only viral infection where post-exposure immunization is helpful. The Ebola virus is the prototypic member of the third family of negative-sense RNA viruses, the Filoviridae. As its name implies, this family consists of viruses with elongated nucleocapsids. Ebola causes outbreaks of severe hemorrhagic fever that is often fatal. Although the disease has not been seen in the U.S., several individuals in Reston, Virginia were infected by an Ebola strain with reduced virulence that was carried in a primate laboratory animal shipment. The bornaviridae make up the final family of this group. These viruses are unique among the negative-sense RNA viruses in that they replicate in the nucleus in order to utilize the cellular splicing machinery. It has been suggested that bornaviruses play a role in several neural pathologies, but their exact contribution to human disease is still being explored.
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