Provirus

4 Key excerpts on "Provirus"

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  Viral Vectors

  Gene Therapy and Neuroscience Applications

  • Michael G. Kaplitt, Arthur D. Loewy(Authors)
  • 1995(Publication Date)
  • Academic Press

    (Publisher)

  5. Genetics and Biology of Retroviral Vectors 79 strains can be xenotropic, in which the virus is unable to infect mouse strains but can infect a wide range of other species; ecotropic, in which viral infection is restricted to mouse cells; or amphotropic, in which viruses can infect both murine and nonmurine cells (Weiss, 1984). Productively infected cells also can be resis- tent to superinfection by the same viral strain by a mechanism in which envelope glycoproteins bind to the cellular virus receptor in the endoplasmic reticulum and thus abrogate superinfection (Delwart and Panganiban, 1989). Upon infection, the single-stranded viral RNA is copied into a double- stranded DNA by reverse transcriptase carried within the virion particle (for a detailed understanding of this mechanism see Gilboa, 1979b). This linear, double-stranded DNA is transported into the nucleus as the precursor to the inte- grated proviral form of the viral DNA (Brown et al., 1987). The virion-supplied IN protein catalyzes removal of two nucleotides from the 3' ends of the linear viral DNA, generation of staggered nicks in the host DNA, and integrative recom- bination resulting in proviral insertion with a short, characteristic duplication of host target sequences at the site of integration (Grandgenett and Mumm, 1990). The site of integration is not entirely random because DNaseI-hypersensi- tive sites are clearly favored, suggesting a preference for integration into open chromatin domains (Rohdewohld et al., 1987). The integrated Provirus then ex- presses the viral genes and new virions are produced constitutively and released from the infected cell without any deleterious effects to the cell itself. A large body of evidence indicates that viral replication, integration, and production of progeny virus depend on host cell progression through the cell cycle. Replication and integration are particularly dependent on cells being in S phase at the time of infection (Varmus and Swanstrom, 1984).

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  Mobile Genetic Elements

  • James Shapiro(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  The progenitor of this sequence is not known, but it is likely that a Provirus was inserted in the satellite DNA and partly excised by homologous recombination between its LTRs (see Fig. 13B) before amplification of the satellite. Retroviruses remain unique among animal viruses in their capacity to be transmitted through the germ line. This property of retroviruses has fostered the notion that Proviruses are normal cellular components (or recent derivatives thereof) and has stimulated speculation about their roles in development, evolu-tion, and disease. Such views should be treated with caution, however, because there is now considerable evidence (reviewed briefly below and more extensively in Coffin, 1982b) suggesting that endogenous Proviruses are most commonly the consequence of rare and usually recent germ line infections. According to the latter perspective, endogenous Proviruses are distinctly viral rather than cellular in character, probably useless and adventitious components of germ lines in most cases, and well tolerated only if relatively innocuous. The most dramatic sup-porting evidence for these conjectures is the complete absence of certain types of chicken or murine retroviruses from the germ lines of a minority of apparently healthy animals (Cohen and Varmus, 1979; Astrin et al., 1979; Frisby et al., 1979; Steffen etal., 1980). 1. DISTRIBUTION AND STRUCTURE The contention that endogenous Proviruses are the residua of relatively recent germ line infections is most strongly supported by two kinds of observations: (7) endogenous Proviruses have all of the structural properties of Proviruses acquired by experimental infection and (2) the distribution of endogenous Proviruses usually shows poor concordance with evolutionary relationships among the hosts. In general, endogenous Proviruses conform to the organizational rules de-scribed earlier for exogenous Proviruses.

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  Molecular Biology

  • David P. Clark(Author)
  • 2009(Publication Date)
  • Academic Cell

    (Publisher)

  Chapter Seventeen

  Viruses

  Viruses are Infectious Packages of Genetic Information Life Cycle of a Virus Bacterial Viruses are Known as Bacteriophage Lysogeny or Latency by Integration The Great Diversity of Viruses Small Single-Stranded DNA Viruses of Bacteria Complex Bacterial Viruses with Double Stranded DNA DNA Viruses of Higher Organisms Viruses with RNA Genomes Have Very Few Genes Bacterial RNA Viruses Double Stranded RNA Viruses of Animals Positive-Stranded RNA Viruses Make Polyproteins Strategy of Negative-Strand RNA Viruses Plant RNA Viruses Retroviruses Use both RNA and DNA Genome of the Retrovirus Subviral Infectious Agents Satellite Viruses Viroids are Naked Molecules of Infectious RNA Prions are Infectious Proteins

  Viruses are Infectious Packages of Genetic Information

  Viruses are packages of genes inside protective shells of protein. Viruses cannot grow or divide alone. In order to replicate, a virus must first infect a host cell. Only then are the virus genes expressed and the virus components manufactured using the host cell machinery. Viruses are not merely pieces of nucleic acid like plasmids or transposons and neither are they true living cells with the ability to generate energy and make protein. They lie in the gray area between. Viruses cannot make their own proteins or generate their own energy. They can only multiply when they have entered a suitable host cell and taken over the cellular machinery. Despite this a virus is certainly not inert; it does replicate if it can subvert a host cell.

  Viruses are sub-cellular parasites that rely on a cell to provide energy and raw material.

  Virus particles contain proteins plus genetic information in the form of DNA or RNA (Fig. 17.01 ). The virus particle, or virion , consists of a protein shell, known as a capsid , surrounding a length of nucleic acid, either RNA or DNA, which carries the virus genes and is often referred to as the viral genome

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  Concepts in Gene Therapy

  • Michael Strauss, John A. Barranger, Michael Strauss, John A. Barranger(Authors)
  • 2020(Publication Date)
  • De Gruyter

    (Publisher)

  I Methods of Gene Delivery 1. Retroviral Vectors Brian Salmons and Walter H. Giinzburg 1.1 Introduction Retroviruses are unique in that they carry two copies of a single stranded RNA genome in the virus particle but, upon infection of a target cell, this RNA is con-verted into a double stranded DNA form and integrated into the target cell genome. The synthesis of viral DNA from RNA is performed by a virally transmitted enzyme activity (reverse transcriptase). A second viral enzyme (integrase) is responsible for the integration of this double stranded DNA form into host cell chromosomal DNA. The integrated DNA form is termed a Provirus. Integration of the Provirus is essen-tially random with respect to the host cell chromosomal DNA, although there may be some preference for actively transcribed regions. A consequence of integration is that the Provirus is stably inherited by all the offspring or daughter cells of the originally infected cell, as if it were a normal cellular gene. It is this property of retroviruses that has made them attractive as the basis of gene transfer vehicles (vectors). Many different retroviruses have been isolated from a wide range of different species, most commonly from mice, birds and cats but also from others including humans. Often they have been isolated because of their association with tumour for-mation. Historically these viruses were divided into acutely transforming and slow transforming viruses. The acutely transforming viruses were found to have acquired cellular genes (oncogenes), which normally play important roles in cell cycle control, in place of one or more viral structural gene, as a result of a rare recombination event. The acquired oncogenes became a stable part of the genetic make-up of these acutely transforming viruses and were transfered, along with the viral genome, into the in-fected target cell.

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