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Development and application of a high-throughput microneutralization assay: lack of xenotropic murine leukemia virus–related virus and/or murine leukemia virus detection in blood donors

Authors

  • Yanchen Zhou,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Imke Steffen,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Leilani Montalvo,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Tzong-Hae Lee,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Reeve Zemel,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • William M. Switzer,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Shaohua Tang,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Hongwei Jia,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Walid Heneine,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Valerie Winkelman,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Chetankumar S. Tailor,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Yasuhiro Ikeda,

    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
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  • Graham Simmons

    Corresponding author
    1. From the Blood Systems Research Institute, and the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California; Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; Creative Testing Solutions, Tempe, Arizona; the Hospital for Sick Children, Toronto, Ontario, Canada; and the Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
      Graham Simmons, Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: gsimmons@bloodsystems.org.
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  • This work was partially funded by a R21 grant from the National Heart, Lung, and Blood Institute (NHLBI) to GS (1R21HL109761). The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of their sponsoring institutions.

Graham Simmons, Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: gsimmons@bloodsystems.org.

Abstract

BACKGROUND: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) and other related MLVs have been described with chronic fatigue syndrome and certain types of prostate cancer. In addition, prevalence rates as high as 7% have been reported in blood donors, raising the risk of transfusion-related transmission. Several laboratories have utilized microneutralization assays as a surrogate marker for detection of anti-MLV serologic responses—with up to 25% of prostate cancer patients reported to harbor neutralizing antibody responses.

STUDY DESIGN AND METHODS: We developed a high-throughput microneutralization assay for research studies on blood donors using retroviral vectors pseudotyped with XMRV-specific envelopes. Infection with these pseudotypes was neutralized by sera from both macaques and mice challenged with XMRV, but not preimmune serum. A total of 354 plasma samples from blood donors in the Reno/Tahoe area were screened for neutralization.

RESULTS: A total of 6.5% of donor samples gave moderate neutralization of XMRV, but not control pseudotypes. However, further testing by Western blot revealed no evidence of antibodies against MLVs in any of these samples. Furthermore, no evidence of infectious virus or viral nucleic acid was observed.

CONCLUSION: A microneutralization assay was developed for detection of XMRV and can be applied in a high-throughput format for large-scale studies. Although a proportion of blood donors demonstrated the ability to block XMRV envelope-mediated infection, we found no evidence that this inhibition was mediated by specific antibodies elicited by exposure to XMRV or MLV. It is likely that this moderate neutralization is mediated through another, nonspecific mechanism.

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