Murine Leukemia Virus

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Myra O Mcclure - One of the best experts on this subject based on the ideXlab platform.

John M Coffin - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of Hortulanus Endogenous Murine Leukemia Virus, an Endogenous ProVirus That Encodes an Infectious Murine Leukemia Virus of a Novel Subgroup
    Journal of Virology, 2005
    Co-Authors: Christopher H. Tipper, Craig E. Bencsics, John M Coffin
    Abstract:

    Simple retroViruses present a unique opportunity for examining the host-Virus relationship. Following exogenous infection and integration into the germ line, copies of these Viruses can become fixed within the genome. The resulting endogenous proviral “fossils” represent a record of past retroviral infections and forms. Previous work in our laboratory has been directed at dissecting the extensive nonecotropic Murine Leukemia Virus content of the mouse genome. One such proVirus, hortulanus endogenous Murine Leukemia Virus (HEMV), found in a single copy in the genome of Mus spicilegus, was remarkable for characteristics that suggested that it was ancient and related to the hypothetical common ancestor of Murine Leukemia Viruses (MLVs) and other gammaretroviral species. In the present study, we have analyzed its functional properties. Transfection of a molecular clone of the HEMV proVirus into mouse-derived cell lines revealed that it is replication competent. Furthermore, host range and interference studies revealed a strictly ecotropic host range and the use of a receptor distinct from those used by other classical MLVs. The identity of nucleotide sequence of the long terminal repeats (LTRs) further suggested that HEMV is a relatively recent insertion into the M. spicilegus genome at the distal end of chromosome 7. Although unique to M. spicilegus, its presence in a homozygous state in three individuals obtained from different regions implies that it has been present long enough to become fixed in this species. Exhaustive phylogenetic analysis of all regions of the HEMV genome supported the previously assigned ancestral position of HEMV relative to other MLV-related Viruses. Thus, HEMV is a relatively recent introduction into the Mus germ line but is representative of a relatively ancestral MLV group.

  • symmetrical base preferences surrounding hiv 1 avian sarcoma leukosis Virus and Murine Leukemia Virus integration sites
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Alexander G Holman, John M Coffin
    Abstract:

    To investigate retroviral integration targeting on a nucleotide scale, we examined the base frequencies directly surrounding cloned in vivo HIV-1, Murine Leukemia Virus, and avian sarcoma/leukosis Virus integrations. Base preferences of up to 2-fold the expected frequencies were found for three Viruses, representing P values down to <10-100 and defining what appear to be preferred integration sequences. Offset symmetry reflecting the topology of the integration reaction was found for HIV-1 and avian sarcoma/leukosis Virus but not Murine Leukemia Virus, suggesting fundamental differences in the way different retroviral integration complexes interact with host-cell DNA.

Lucinda Bateman - One of the best experts on this subject based on the ideXlab platform.

  • no association found between the detection of either xenotropic Murine Leukemia Virus related Virus or polytropic Murine Leukemia Virus and chronic fatigue syndrome in a blinded multi site prospective study by the establishment and use of the solvecf
    BMC Research Notes, 2014
    Co-Authors: David M Irlbeck, Suzanne D Vernon, Kimberly Mccleary, Lucinda Bateman, Nancy G Klimas, Charles W Lapp, Daniel L Peterson, James R Brown, Katja Remlinger, David A Wilfret
    Abstract:

    Background In 2009, a retrospective study reported the detection of xenotropic Murine Leukemia Virus-related Virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic Murine Leukemia Virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these Viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates.

  • a multicenter blinded analysis indicates no association between chronic fatigue syndrome myalgic encephalomyelitis and either xenotropic Murine Leukemia Virus related Virus or polytropic Murine Leukemia Virus
    Mbio, 2012
    Co-Authors: Harvey J Alter, Lucinda Bateman, Nancy G Klimas, Judy A Mikovits, William M Switzer, Francis W Ruscetti, Shyhching Lo, Anthony L Komaroff, Jose G Montoya, Susan Levine
    Abstract:

    The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic Murine Leukemia Virus-related Virus (XMRV) and polytropic Murine leu- kemia Virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients con- tinue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic Murine Leukemia Virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for patho- gen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rap- idly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in thisfield.

  • absence of xmrv retroVirus and other Murine Leukemia Virus related Viruses in patients with chronic fatigue syndrome
    Journal of Virology, 2011
    Co-Authors: Clifford Shin, Lucinda Bateman, Robert Schlaberg, Ashley M Bunker, Christopher J Leonard, Ronald W Hughen, Alan R Light, Kathleen C Light, Ila R Singh
    Abstract:

    Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic Murine Leukemia Virus-related Virus (XMRV) as well as other Murine Leukemia Virus (MLV)-related Viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious Viruses, nor did we find antibodies to these Viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related Viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

Vinay K Pathak - One of the best experts on this subject based on the ideXlab platform.

  • lack of detection of xenotropic Murine Leukemia Virus related Virus in hiv 1 lymphoma patients
    Advances in Virology, 2011
    Co-Authors: Krista A Delviksfrankenberry, Chawaree Chaipan, Rachel Bagni, Kathleen M Wyvill, Robert Yarchoan, Vinay K Pathak
    Abstract:

    Xenotropic Murine Leukemia Virus-related Virus (XMRV) is a gammaretroVirus reported to be associated with human prostate cancer and chronic fatigue syndrome. Since retroViruses cause various cancers, and XMRV replication might be facilitated by HIV-1 co-infection, we asked whether certain patients with HIV-associated lymphomas are infected with XMRV. Analysis of PMBCs and plasma from 26 patients failed to detect XMRV by PCR, ELISA, or Western blot, suggesting a lack of association between XMRV and AIDS-associated lymphomas.

  • inhibition of xenotropic Murine Leukemia Virus related Virus by apobec3 proteins and antiviral drugs
    Journal of Virology, 2010
    Co-Authors: Tobias Paprotka, Krista A Delviksfrankenberry, Chawaree Chaipan, Narasimhan J Venkatachari, Ryan C Burdick, Weishau Hu, Vinay K Pathak
    Abstract:

    Xenotropic Murine Leukemia Virus-related Virus (XMRV), a gammaretroVirus, has been isolated from human prostate cancer tissue and from activated CD4+ T cells and B cells of patients with chronic fatigue syndrome, suggesting an association between XMRV infection and these two diseases. Since APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of Murine Leukemia Virus and Vif-deficient human immunodeficiency Virus type 1 (HIV-1), are expressed in human CD4+ T cells and B cells, we sought to determine how XMRV evades suppression of replication by APOBEC3 proteins. We found that expression of A3G, A3F, or Murine A3 in Virus-producing cells resulted in their virion incorporation, inhibition of XMRV replication, and G-to-A hypermutation of the viral DNA with all three APOBEC3 proteins. Quantitation of A3G and A3F mRNAs indicated that, compared to the human T-cell lines CEM and H9, prostate cell lines LNCaP and DU145 exhibited 50% lower A3F mRNA levels, whereas A3G expression in 22Rv1, LNCaP, and DU145 cells was nearly undetectable. XMRV proviral genomes in LNCaP and DU145 cells were hypermutated at low frequency with mutation patterns consistent with A3F activity. XMRV proviral genomes were extensively hypermutated upon replication in A3G/A3F-positive T cells (CEM and H9), but not in A3G/A3F-negative cells (CEM-SS). We also observed that XMRV replication was susceptible to the nucleoside reverse transcriptase (RT) inhibitors zidovudine (AZT) and tenofovir and the integrase inhibitor raltegravir. In summary, the establishment of XMRV infection in patients may be dependent on infection of A3G/A3F-deficient cells, and cells expressing low levels of A3G/A3F, such as prostate cancer cells, may be ideal producers of infectious XMRV. Furthermore, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV infection.

Camille N Kotton - One of the best experts on this subject based on the ideXlab platform.