alexa Retroviral Virions and Genomes.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacovigilance

Author(s): Authors Vogt VM

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Excerpt For all viruses, the structure of the viral particle (virion) in part reflects the fundamental requirements imposed by the need for propagation. These requirements include incorporation of the genome into particles that are stable outside of cells, recognition of and entry into appropriate host cells, replication of the genome, and the translation of viral messenger RNA to yield new viral proteins. Retroviruses are enveloped RNA viruses, a complex group with several common features. Enveloped RNA viruses contain proteins that carry out five basic functions: (1) condensation of the genome into an RNA-protein complex; (2) packaging of this complex in a protein shell; (3) enclosure of the shell in a lipid membrane, or envelope; (4) modification of the envelope by addition of surface proteins that recognize cellular receptors; and (5) for negative strand viruses and retroviruses, copying of the RNA in the newly infected cell. Many enveloped viruses in fact are more complicated, with two or more proteins sharing each function, and others are simpler, with one protein carrying out two or three functions. The simpler enveloped viruses provide useful paradigms to help understand aspects of retroviral structure. Until the successful crystallization and X-ray diffraction work on spherical viruses in the last decade, structural information was gained largely by fractionation of the components of purified viruses, by electron microscopy, and indirectly by genetic analysis. For the many viruses for which useful crystals have not been obtained, these techniques remain the cornerstone upon which inferences about structure are built. The first direct visualization of retroviruses, by thin-section and negative-stain electron microscopy, predated these first biochemical studies (Bernhard 1958). The first substantially pure preparations of retroviruses became available in the 1960s, for the avian sarcoma/leukosis viruses (ASLVs) and the murine leukemia viruses (MLVs), which were the most widely studied retroviruses until the advent of human immunodeficiency virus (HIV). The technique of SDS-polyacrylamide gel electrophoresis to separate denatured polypeptides, developed in the late 1960s, became a key tool to characterize the viral proteins. Discovery of viral reverse transcriptase (Baltimore 1970; Temin and Mizutani 1970) and its associated RNase H (Moelling et al. 1971) and elucidation of the mechanism by which the genome is copied (Chapter 4) provided a unifying simplicity to models for replication. Also unifying was the recognition that the internal structural proteins are derived from a precursor polypeptide (Vogt and Eisenman 1973) and that the reverse transcriptase itself, as well as the protease necessary for processing of the precursor, is translated as a precursor also containing the structural proteins (Chapter 7). The much later observation that the virus carries with it the enzyme-catalyzing integration of viral DNA into host chromosomes (Chapter 5) further solidified the view of retroviral structure and replication. Finally, the discoveries that retroviral transformation is genetically separable from replication and that retroviral oncogenes are derived directly from cellular oncogenes (Chapter 10) made it clear that the complexities of oncogenic transformation in many cases had little to do with the virus per se. One might say that this theme of simplicity survived until the discovery of retroviral accessory genes in human T-cell leukemia virus (HTLV) (Seiki et al. 1983), eventually extended to HIV and other viruses (Chapter 6). Even so, in terms of structural and genetic organization, retroviruses remain among the simpler members of the virus world, and they are likely to be among the more ancient as well (Chapter 8). Copyright © 1997, Cold Spring Harbor Laboratory Press.
This article was published in Retroviral Virions and Genomes and referenced in Journal of Pharmacovigilance

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