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      Murine Leukemia Viruses: Objects and Organisms

      review-article
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      Advances in Virology
      Hindawi Publishing Corporation

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          Abstract

          Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes—protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera.

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          Most cited references141

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          Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu.

          Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.
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            Retroviral restriction by APOBEC proteins.

            A powerful mechanism of vertebrate innate immunity has been discovered in the past year, in which APOBEC proteins inhibit retroviruses by deaminating cytosine residues in nascent retroviral cDNA. To thwart this cellular defence, HIV encodes Vif, a small protein that mediates APOBEC degradation. Therefore, the balance between APOBECs and Vif might be a crucial determinant of the outcome of retroviral infection. Vertebrates have up to 11 different APOBEC proteins, with primates having the most. APOBEC proteins include AID, a probable DNA mutator that is responsible for immunoglobulin-gene diversification, and APOBEC1, an RNA editor with antiretroviral activities. This APOBEC abundance might help to tip the balance in favour of cellular defences.
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              Integration of murine leukemia virus DNA depends on mitosis.

              In synchronized rat or mouse cells infected with Moloney murine leukemia virus (MLV), integration of viral DNA and production of viral proteins occur only after the cells traverse mitosis. Integration is blocked when cells are prevented from progressing through mitosis. Viral nucleoprotein complexes isolated from arrested cells contain full-length viral DNA and can integrate this viral DNA in vitro, showing that the block to integration in arrested cells is not due to a lack of mature integration machinery. When infected cells traverse mitosis, there is a sharp increase in nuclear accumulation of viral DNA. The dependence of integration on mitosis may therefore be due to a requirement for mitosis and nuclear envelope breakdown for entry of the viral integration complex into the nucleus.
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                Author and article information

                Journal
                Adv Virol
                AV
                Advances in Virology
                Hindawi Publishing Corporation
                1687-8639
                1687-8647
                2011
                15 November 2011
                : 2011
                : 403419
                Affiliations
                HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA
                Author notes

                Academic Editor: Arifa S. Khan

                Article
                10.1155/2011/403419
                3265304
                22312342
                fee164aa-e19e-43de-a231-af9ba635b334
                Copyright © 2011 Alan Rein.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 June 2011
                : 25 July 2011
                Categories
                Review Article

                Microbiology & Virology
                Microbiology & Virology

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