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
Identifieur interne : 001F05 ( Main/Exploration ); précédent : 001F04; suivant : 001F06Development 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
Auteurs : Yanchen Zhou [États-Unis] ; Imke Steffen [États-Unis] ; Leilani Montalvo [États-Unis] ; Tzong-Hae Lee [États-Unis] ; Reeve Zemel [États-Unis] ; William M. Switzer [États-Unis] ; Shaohua Tang [États-Unis] ; Hongwei Jia [États-Unis] ; Walid Heneine [États-Unis] ; Valerie Winkelman [États-Unis] ; Chetankumar S. Tailor [États-Unis] ; Yasuhiro Ikeda [États-Unis] ; Graham Simmons [États-Unis]Source :
- Transfusion [ 0041-1132 ] ; 2012-02.
English descriptors
- Teeft :
- Acad, Assay, Assay system, Blood cells, Blood donor sera, Blood donors, Blood systems research institute, Chronic fatigue syndrome, Clear neutralization, Donor, Donor plasma, Donor samples, Donor sera, Encoding, February, Glycoprotein, Lacz, Lacz encoding, Leukemia, Lncap, Lncap cells, Lombardi, Luciferase, Macaque, Microneutralization, Microneutralization assay, Mlvs, Moderate neutralization, Murine, Natl, Neutralization, Neutralizing, Other mlvs, Plasmid, Positive control, Positive controls, Primer, Primer pairs, Proc, Proc natl acad, Prostate, Prostate cancer, Prostate cells, Pseudotyped, Pseudoviruses, Retroviral, Retroviral backbone, Retrovirology, Retrovirus, Rhesus macaques, Serologic, Serologic evidence, Serologic response, Syndrome, Transfusion, Transfusion volume, Viral, Viral envelope, Viral infection, Virol, Virus, Western blot, Xenotropic, Xmrv, Xmrv detection, Xmrv infection, Zhou.
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.
Url:
DOI: 10.1111/j.1537-2995.2011.03519.x
Affiliations:
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Switzer</name></author><author><name sortKey="Tang, Shaohua" sort="Tang, Shaohua" uniqKey="Tang S" first="Shaohua" last="Tang">Shaohua Tang</name></author><author><name sortKey="Jia, Hongwei" sort="Jia, Hongwei" uniqKey="Jia H" first="Hongwei" last="Jia">Hongwei Jia</name></author><author><name sortKey="Heneine, Walid" sort="Heneine, Walid" uniqKey="Heneine W" first="Walid" last="Heneine">Walid Heneine</name></author><author><name sortKey="Winkelman, Valerie" sort="Winkelman, Valerie" uniqKey="Winkelman V" first="Valerie" last="Winkelman">Valerie Winkelman</name></author><author><name sortKey="Tailor, Chetankumar S" sort="Tailor, Chetankumar S" uniqKey="Tailor C" first="Chetankumar S." last="Tailor">Chetankumar S. 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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</wicri:cityArea></affiliation></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Montalvo, Leilani" sort="Montalvo, Leilani" uniqKey="Montalvo L" first="Leilani" last="Montalvo">Leilani Montalvo</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Lee, Tzong Ae" sort="Lee, Tzong Ae" uniqKey="Lee T" first="Tzong-Hae" last="Lee">Tzong-Hae Lee</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Zemel, Reeve" sort="Zemel, Reeve" uniqKey="Zemel R" first="Reeve" last="Zemel">Reeve Zemel</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Switzer, William M" sort="Switzer, William M" uniqKey="Switzer W" first="William M." last="Switzer">William M. Switzer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Tang, Shaohua" sort="Tang, Shaohua" uniqKey="Tang S" first="Shaohua" last="Tang">Shaohua Tang</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Jia, Hongwei" sort="Jia, Hongwei" uniqKey="Jia H" first="Hongwei" last="Jia">Hongwei Jia</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Heneine, Walid" sort="Heneine, Walid" uniqKey="Heneine W" first="Walid" last="Heneine">Walid Heneine</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Winkelman, Valerie" sort="Winkelman, Valerie" uniqKey="Winkelman V" first="Valerie" last="Winkelman">Valerie Winkelman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Tailor, Chetankumar S" sort="Tailor, Chetankumar S" uniqKey="Tailor C" first="Chetankumar S." last="Tailor">Chetankumar S. Tailor</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Ikeda, Yasuhiro" sort="Ikeda, Yasuhiro" uniqKey="Ikeda Y" first="Yasuhiro" last="Ikeda">Yasuhiro Ikeda</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation></author><author><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>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</wicri:cityArea></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Transfusion</title><title level="j" type="alt">TRANSFUSION</title><idno type="ISSN">0041-1132</idno><idno type="eISSN">1537-2995</idno><imprint><biblScope unit="vol">52</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="332">332</biblScope><biblScope unit="page" to="342">342</biblScope><biblScope unit="page-count">11</biblScope><publisher>Blackwell Publishing Inc</publisher><pubPlace>Malden, USA</pubPlace><date type="published" when="2012-02">2012-02</date></imprint><idno type="ISSN">0041-1132</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0041-1132</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acad</term><term>Assay</term><term>Assay system</term><term>Blood cells</term><term>Blood donor sera</term><term>Blood donors</term><term>Blood systems research institute</term><term>Chronic fatigue syndrome</term><term>Clear neutralization</term><term>Donor</term><term>Donor plasma</term><term>Donor samples</term><term>Donor sera</term><term>Encoding</term><term>February</term><term>Glycoprotein</term><term>Lacz</term><term>Lacz encoding</term><term>Leukemia</term><term>Lncap</term><term>Lncap cells</term><term>Lombardi</term><term>Luciferase</term><term>Macaque</term><term>Microneutralization</term><term>Microneutralization assay</term><term>Mlvs</term><term>Moderate neutralization</term><term>Murine</term><term>Natl</term><term>Neutralization</term><term>Neutralizing</term><term>Other mlvs</term><term>Plasmid</term><term>Positive control</term><term>Positive controls</term><term>Primer</term><term>Primer pairs</term><term>Proc</term><term>Proc natl acad</term><term>Prostate</term><term>Prostate cancer</term><term>Prostate cells</term><term>Pseudotyped</term><term>Pseudoviruses</term><term>Retroviral</term><term>Retroviral backbone</term><term>Retrovirology</term><term>Retrovirus</term><term>Rhesus macaques</term><term>Serologic</term><term>Serologic evidence</term><term>Serologic response</term><term>Syndrome</term><term>Transfusion</term><term>Transfusion volume</term><term>Viral</term><term>Viral envelope</term><term>Viral infection</term><term>Virol</term><term>Virus</term><term>Western blot</term><term>Xenotropic</term><term>Xmrv</term><term>Xmrv detection</term><term>Xmrv infection</term><term>Zhou</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Minnesota</li></region></list><tree><country name="États-Unis"><region name="Minnesota"><name sortKey="Zhou, Yanchen" sort="Zhou, Yanchen" uniqKey="Zhou Y" first="Yanchen" last="Zhou">Yanchen Zhou</name></region><name sortKey="Heneine, Walid" sort="Heneine, Walid" uniqKey="Heneine W" first="Walid" last="Heneine">Walid Heneine</name><name sortKey="Ikeda, Yasuhiro" sort="Ikeda, Yasuhiro" uniqKey="Ikeda Y" first="Yasuhiro" last="Ikeda">Yasuhiro Ikeda</name><name sortKey="Jia, Hongwei" sort="Jia, Hongwei" uniqKey="Jia H" first="Hongwei" last="Jia">Hongwei Jia</name><name sortKey="Lee, Tzong Ae" sort="Lee, Tzong Ae" uniqKey="Lee T" first="Tzong-Hae" last="Lee">Tzong-Hae Lee</name><name sortKey="Montalvo, Leilani" sort="Montalvo, Leilani" uniqKey="Montalvo L" first="Leilani" last="Montalvo">Leilani Montalvo</name><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name><name sortKey="Switzer, William M" sort="Switzer, William M" uniqKey="Switzer W" first="William M." last="Switzer">William M. Switzer</name><name sortKey="Tailor, Chetankumar S" sort="Tailor, Chetankumar S" uniqKey="Tailor C" first="Chetankumar S." last="Tailor">Chetankumar S. Tailor</name><name sortKey="Tang, Shaohua" sort="Tang, Shaohua" uniqKey="Tang S" first="Shaohua" last="Tang">Shaohua Tang</name><name sortKey="Winkelman, Valerie" sort="Winkelman, Valerie" uniqKey="Winkelman V" first="Valerie" last="Winkelman">Valerie Winkelman</name><name sortKey="Zemel, Reeve" sort="Zemel, Reeve" uniqKey="Zemel R" first="Reeve" last="Zemel">Reeve Zemel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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