Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA.
Journal of Virology (Impact Factor: 4.44). 03/2009; 83(6):2429-35. DOI: 10.1128/JVI.01926-08
Source: PubMed


Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

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Available from: Kimmo Virtaneva
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    • "There is growing evidence and appreciation of the interaction between germline endogenous retrotransposable elements (ERE) and exogenous retroviruses in multiple species. In mice, infection with exogenous ectopic MuLV results in replication of defective endogenous polytopic retroviruses [1]. We, and others, have observed that certain ERE including specific human endogenous retrovirus (HERV) families [2]–[11] and long interspersed nuclear element (LINE)-1 insertions [12], which normally remain dormant in healthy somatic cells, are activated following HIV infection. "
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    • "First, P-MLVs are generally transmitted in viremic mice as pseudotypes of E-MLVs and thus use mCAT-1 for entry [114, 115]. Also, homodimers representing the transcribed products of Mpmv and Pmv proviruses can be packaged into E-MLV virions, and these “mobilized” proviruses can infect cells, replicate in those new cells, and spread to other cells as pseudotyped virus [116]. Another transmission mechanism allows infectious, recombinant P-MLVs to use alternative receptors in the presence of the soluble RBD glycoprotein for that receptor. "
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    ABSTRACT: Gammaretroviruses of several different host range subgroups have been isolated from laboratory mice. The ecotropic viruses infect mouse cells and rely on the host CAT-1 receptor. The xenotropic/polytropic viruses, and the related human-derived XMRV, can infect cells of other mammalian species and use the XPR1 receptor for entry. The coevolution of these viruses and their receptors in infected mouse populations provides a good example of how genetic conflicts can drive diversifying selection. Genetic and epigenetic variations in the virus envelope glycoproteins can result in altered host range and pathogenicity, and changes in the virus binding sites of the receptors are responsible for host restrictions that reduce virus entry or block it altogether. These battleground regions are marked by mutational changes that have produced 2 functionally distinct variants of the CAT-1 receptor and 5 variants of the XPR1 receptor in mice, as well as a diverse set of infectious viruses, and several endogenous retroviruses coopted by the host to interfere with entry.
    Full-text · Article · Oct 2011 · Advances in Virology
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    • "Mammalian genomes harbor a large number of retroviral elements, many of which are defective, although some contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. Mobilization of an endogenous retrovirus upon infection with an exogenous retrovirus may have profound effects on the pathogenesis of a retrovirus infection (Evans et al., 2009). @BULLET H Human endogenous retroviruses (HERVs) result from ancestral infection by infectious viruses over millions of years of primate evolution. "

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