Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1
Identifieur interne : 000665 ( Pmc/Curation ); précédent : 000664; suivant : 000666Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1
Auteurs : Kenta Iijima [Japon] ; Noriyuki Okudaira [Japon] ; Masato Tamura [Japon] ; Akihiro Doi [Japon] ; Yoshikazu Saito [Japon] ; Mari Shimura [Japon] ; Motohito Goto [Japon] ; Akihiro Matsunaga [Japon] ; Yuki I. Kawamura [Japon] ; Takeshi Otsubo [Japon] ; Taeko Dohi [Japon] ; Shigeki Hoshino [Japon] ; Shigeyuki Kano [Japon] ; Shotaro Hagiwara [Japon] ; Junko Tanuma [Japon] ; Hiroyuki Gatanaga [Japon] ; Masanori Baba [Japon] ; Taku Iguchi [Japon] ; Motoko Yanagita [Japon] ; Shinichi Oka [Japon] ; Tadashi Okamura [Japon] ; Yukihito Ishizaka [Japon]Source :
- Retrovirology [ 1742-4690 ] ; 2013.
Abstract
Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the
We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice.
Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases.
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DOI: 10.1186/1742-4690-10-83
PubMed: 23915234
PubMed Central: 3751050
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Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I11">Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa- cho, Nishinomiya, Hyogo 663-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Legal Medicine, Hyogo College of 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Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation></author><author><name sortKey="Saito, Yoshikazu" sort="Saito, Yoshikazu" uniqKey="Saito Y" first="Yoshikazu" last="Saito">Yoshikazu Saito</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country 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Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Matsunaga, Akihiro" sort="Matsunaga, Akihiro" uniqKey="Matsunaga A" first="Akihiro" last="Matsunaga">Akihiro Matsunaga</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Kawamura, Yuki I" sort="Kawamura, Yuki I" uniqKey="Kawamura Y" first="Yuki I" last="Kawamura">Yuki I. Kawamura</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Otsubo, Takeshi" sort="Otsubo, Takeshi" uniqKey="Otsubo T" first="Takeshi" last="Otsubo">Takeshi Otsubo</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Dohi, Taeko" sort="Dohi, Taeko" uniqKey="Dohi T" first="Taeko" last="Dohi">Taeko Dohi</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Hoshino, Shigeki" sort="Hoshino, Shigeki" uniqKey="Hoshino S" first="Shigeki" last="Hoshino">Shigeki Hoshino</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Kano, Shigeyuki" sort="Kano, Shigeyuki" uniqKey="Kano S" first="Shigeyuki" last="Kano">Shigeyuki Kano</name><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Hagiwara, Shotaro" sort="Hagiwara, Shotaro" uniqKey="Hagiwara S" first="Shotaro" last="Hagiwara">Shotaro Hagiwara</name><affiliation wicri:level="1"><nlm:aff id="I6">Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Tanuma, Junko" sort="Tanuma, Junko" uniqKey="Tanuma J" first="Junko" last="Tanuma">Junko Tanuma</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Gatanaga, Hiroyuki" sort="Gatanaga, Hiroyuki" uniqKey="Gatanaga H" first="Hiroyuki" last="Gatanaga">Hiroyuki Gatanaga</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Baba, Masanori" sort="Baba, Masanori" uniqKey="Baba M" first="Masanori" last="Baba">Masanori Baba</name><affiliation wicri:level="1"><nlm:aff id="I8">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544</wicri:regionArea></affiliation></author><author><name sortKey="Iguchi, Taku" sort="Iguchi, Taku" uniqKey="Iguchi T" first="Taku" last="Iguchi">Taku Iguchi</name><affiliation wicri:level="1"><nlm:aff id="I9">Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I12">Kyoto University, Graduate School of Medicine, Medical Innovation Center, Shogoin-Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Kyoto University, Graduate School of Medicine, Medical Innovation Center, Shogoin-Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation></author><author><name sortKey="Yanagita, Motoko" sort="Yanagita, Motoko" uniqKey="Yanagita M" first="Motoko" last="Yanagita">Motoko Yanagita</name><affiliation wicri:level="1"><nlm:aff id="I9">Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation></author><author><name sortKey="Oka, Shinichi" sort="Oka, Shinichi" uniqKey="Oka S" first="Shinichi" last="Oka">Shinichi Oka</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Okamura, Tadashi" sort="Okamura, Tadashi" uniqKey="Okamura T" first="Tadashi" last="Okamura">Tadashi Okamura</name><affiliation wicri:level="1"><nlm:aff id="I3">Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I10">Section of Animal Model, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Section of Animal Model, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Ishizaka, Yukihito" sort="Ishizaka, Yukihito" uniqKey="Ishizaka Y" first="Yukihito" last="Ishizaka">Yukihito Ishizaka</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23915234</idno><idno type="pmc">3751050</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751050</idno><idno type="RBID">PMC:3751050</idno><idno type="doi">10.1186/1742-4690-10-83</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000665</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000665</idno><idno type="wicri:Area/Pmc/Curation">000665</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000665</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1</title><author><name sortKey="Iijima, Kenta" sort="Iijima, Kenta" uniqKey="Iijima K" first="Kenta" last="Iijima">Kenta Iijima</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Okudaira, Noriyuki" sort="Okudaira, Noriyuki" uniqKey="Okudaira N" first="Noriyuki" last="Okudaira">Noriyuki Okudaira</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I11">Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa- cho, Nishinomiya, Hyogo 663-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa- cho, Nishinomiya, Hyogo 663-8501</wicri:regionArea></affiliation></author><author><name sortKey="Tamura, Masato" sort="Tamura, Masato" uniqKey="Tamura M" first="Masato" last="Tamura">Masato Tamura</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Doi, Akihiro" sort="Doi, Akihiro" uniqKey="Doi A" first="Akihiro" last="Doi">Akihiro Doi</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation></author><author><name sortKey="Saito, Yoshikazu" sort="Saito, Yoshikazu" uniqKey="Saito Y" first="Yoshikazu" last="Saito">Yoshikazu Saito</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Shimura, Mari" sort="Shimura, Mari" uniqKey="Shimura M" first="Mari" last="Shimura">Mari Shimura</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Goto, Motohito" sort="Goto, Motohito" uniqKey="Goto M" first="Motohito" last="Goto">Motohito Goto</name><affiliation wicri:level="1"><nlm:aff id="I3">Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Matsunaga, Akihiro" sort="Matsunaga, Akihiro" uniqKey="Matsunaga A" first="Akihiro" last="Matsunaga">Akihiro Matsunaga</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Kawamura, Yuki I" sort="Kawamura, Yuki I" uniqKey="Kawamura Y" first="Yuki I" last="Kawamura">Yuki I. Kawamura</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Otsubo, Takeshi" sort="Otsubo, Takeshi" uniqKey="Otsubo T" first="Takeshi" last="Otsubo">Takeshi Otsubo</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Dohi, Taeko" sort="Dohi, Taeko" uniqKey="Dohi T" first="Taeko" last="Dohi">Taeko Dohi</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516</wicri:regionArea></affiliation></author><author><name sortKey="Hoshino, Shigeki" sort="Hoshino, Shigeki" uniqKey="Hoshino S" first="Shigeki" last="Hoshino">Shigeki Hoshino</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Kano, Shigeyuki" sort="Kano, Shigeyuki" uniqKey="Kano S" first="Shigeyuki" last="Kano">Shigeyuki Kano</name><affiliation wicri:level="1"><nlm:aff id="I2">Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Hagiwara, Shotaro" sort="Hagiwara, Shotaro" uniqKey="Hagiwara S" first="Shotaro" last="Hagiwara">Shotaro Hagiwara</name><affiliation wicri:level="1"><nlm:aff id="I6">Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Tanuma, Junko" sort="Tanuma, Junko" uniqKey="Tanuma J" first="Junko" last="Tanuma">Junko Tanuma</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Gatanaga, Hiroyuki" sort="Gatanaga, Hiroyuki" uniqKey="Gatanaga H" first="Hiroyuki" last="Gatanaga">Hiroyuki Gatanaga</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Baba, Masanori" sort="Baba, Masanori" uniqKey="Baba M" first="Masanori" last="Baba">Masanori Baba</name><affiliation wicri:level="1"><nlm:aff id="I8">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544</wicri:regionArea></affiliation></author><author><name sortKey="Iguchi, Taku" sort="Iguchi, Taku" uniqKey="Iguchi T" first="Taku" last="Iguchi">Taku Iguchi</name><affiliation wicri:level="1"><nlm:aff id="I9">Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I12">Kyoto University, Graduate School of Medicine, Medical Innovation Center, Shogoin-Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Kyoto University, Graduate School of Medicine, Medical Innovation Center, Shogoin-Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation></author><author><name sortKey="Yanagita, Motoko" sort="Yanagita, Motoko" uniqKey="Yanagita M" first="Motoko" last="Yanagita">Motoko Yanagita</name><affiliation wicri:level="1"><nlm:aff id="I9">Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507</wicri:regionArea></affiliation></author><author><name sortKey="Oka, Shinichi" sort="Oka, Shinichi" uniqKey="Oka S" first="Shinichi" last="Oka">Shinichi Oka</name><affiliation wicri:level="1"><nlm:aff id="I7">AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Okamura, Tadashi" sort="Okamura, Tadashi" uniqKey="Okamura T" first="Tadashi" last="Okamura">Tadashi Okamura</name><affiliation wicri:level="1"><nlm:aff id="I3">Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I10">Section of Animal Model, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Section of Animal Model, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author><author><name sortKey="Ishizaka, Yukihito" sort="Ishizaka, Yukihito" uniqKey="Ishizaka Y" first="Yukihito" last="Ishizaka">Yukihito Ishizaka</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655</wicri:regionArea></affiliation></author></analytic><series><title level="j">Retrovirology</title><idno type="eISSN">1742-4690</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the <italic>in vivo</italic> effects of recombinant Vpr (rVpr) by administrating it to transgenic mice harboring human L1 as a transgene (hL1-Tg mice). Based on our data, we discuss the involvement of blood Vpr in the clinical symptoms of acquired immunodeficiency syndrome (AIDS).</p></sec><sec><title>Results</title><p>We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice.</p></sec><sec><title>Conclusions</title><p>Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cohen, Ea" uniqKey="Cohen E">EA Cohen</name></author><author><name sortKey="Dehni, G" uniqKey="Dehni G">G Dehni</name></author><author><name sortKey="Sodroski, Jg" uniqKey="Sodroski J">JG Sodroski</name></author><author><name sortKey="Haseltine, Wa" uniqKey="Haseltine W">WA Haseltine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kogan, M" uniqKey="Kogan M">M Kogan</name></author><author><name sortKey="Rappaport, J" uniqKey="Rappaport J">J Rappaport</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levy, Dn" uniqKey="Levy D">DN Levy</name></author><author><name sortKey="Refaeli, Y" uniqKey="Refaeli Y">Y 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Retrovirology</journal-id><journal-id journal-id-type="iso-abbrev">Retrovirology</journal-id><journal-title-group><journal-title>Retrovirology</journal-title></journal-title-group><issn pub-type="epub">1742-4690</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23915234</article-id><article-id pub-id-type="pmc">3751050</article-id><article-id pub-id-type="publisher-id">1742-4690-10-83</article-id><article-id pub-id-type="doi">10.1186/1742-4690-10-83</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories><title-group><article-title>Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes" id="A1"><name><surname>Iijima</surname><given-names>Kenta</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>kiijima@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" equal-contrib="yes" id="A2"><name><surname>Okudaira</surname><given-names>Noriyuki</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I11">11</xref><email>noku@hyo-med.ac.jp</email></contrib><contrib contrib-type="author" id="A3"><name><surname>Tamura</surname><given-names>Masato</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>mtamura@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A4"><name><surname>Doi</surname><given-names>Akihiro</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><email>adoi@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A5"><name><surname>Saito</surname><given-names>Yoshikazu</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>yosaito@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A6"><name><surname>Shimura</surname><given-names>Mari</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>mshimura@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A7"><name><surname>Goto</surname><given-names>Motohito</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>mgoto@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A8"><name><surname>Matsunaga</surname><given-names>Akihiro</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>amatsunaga@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A9"><name><surname>Kawamura</surname><given-names>Yuki I</given-names></name><xref ref-type="aff" rid="I4">4</xref><email>kawamura@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A10"><name><surname>Otsubo</surname><given-names>Takeshi</given-names></name><xref ref-type="aff" rid="I4">4</xref><email>totsubo@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A11"><name><surname>Dohi</surname><given-names>Taeko</given-names></name><xref ref-type="aff" rid="I4">4</xref><email>dohi@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A12"><name><surname>Hoshino</surname><given-names>Shigeki</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>shigehsn@mac.com</email></contrib><contrib contrib-type="author" id="A13"><name><surname>Kano</surname><given-names>Shigeyuki</given-names></name><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I5">5</xref><email>kano@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A14"><name><surname>Hagiwara</surname><given-names>Shotaro</given-names></name><xref ref-type="aff" rid="I6">6</xref><email>shagiwar@hosp.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A15"><name><surname>Tanuma</surname><given-names>Junko</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>jtanuma@acc.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A16"><name><surname>Gatanaga</surname><given-names>Hiroyuki</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>higatana@acc.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A17"><name><surname>Baba</surname><given-names>Masanori</given-names></name><xref ref-type="aff" rid="I8">8</xref><email>m-baba@m2.kufm.kagoshima-u.ac.jp</email></contrib><contrib contrib-type="author" id="A18"><name><surname>Iguchi</surname><given-names>Taku</given-names></name><xref ref-type="aff" rid="I9">9</xref><xref ref-type="aff" rid="I12">12</xref><email>iguchi@tmk.med.kyoto-u.ac.jp</email></contrib><contrib contrib-type="author" id="A19"><name><surname>Yanagita</surname><given-names>Motoko</given-names></name><xref ref-type="aff" rid="I9">9</xref><email>motoy@kuhp.kyoto-u.ac.jp</email></contrib><contrib contrib-type="author" id="A20"><name><surname>Oka</surname><given-names>Shinichi</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>oka@acc.ncgm.go.jp</email></contrib><contrib contrib-type="author" id="A21"><name><surname>Okamura</surname><given-names>Tadashi</given-names></name><xref ref-type="aff" rid="I3">3</xref><xref ref-type="aff" rid="I10">10</xref><email>okamurat@ri.ncgm.go.jp</email></contrib><contrib contrib-type="author" corresp="yes" id="A22"><name><surname>Ishizaka</surname><given-names>Yukihito</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>zakay@ri.ncgm.go.jp</email></contrib></contrib-group><aff id="I1"><label>1</label>Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I2"><label>2</label>Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan</aff><aff id="I3"><label>3</label>Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I4"><label>4</label>Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan</aff><aff id="I5"><label>5</label>Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I6"><label>6</label>Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I7"><label>7</label>AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I8"><label>8</label>Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan</aff><aff id="I9"><label>9</label>Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan</aff><aff id="I10"><label>10</label>Section of Animal Model, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan</aff><aff id="I11"><label>11</label>Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa- cho, Nishinomiya, Hyogo 663-8501, Japan</aff><aff id="I12"><label>12</label>Kyoto University, Graduate School of Medicine, Medical Innovation Center, Shogoin-Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan</aff><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>5</day><month>8</month><year>2013</year></pub-date><volume>10</volume><fpage>83</fpage><lpage>83</lpage><history><date date-type="received"><day>16</day><month>11</month><year>2012</year></date><date date-type="accepted"><day>18</day><month>7</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Iijima et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>Iijima et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri xlink:href="http://www.retrovirology.com/content/10/1/83"></self-uri><abstract><sec><title>Background</title><p>Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the <italic>in vivo</italic> effects of recombinant Vpr (rVpr) by administrating it to transgenic mice harboring human L1 as a transgene (hL1-Tg mice). Based on our data, we discuss the involvement of blood Vpr in the clinical symptoms of acquired immunodeficiency syndrome (AIDS).</p></sec><sec><title>Results</title><p>We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice.</p></sec><sec><title>Conclusions</title><p>Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases.</p></sec></abstract><kwd-group><kwd>HIV-1</kwd><kwd>Vpr</kwd><kwd>Blood</kwd><kwd>Retrotransposition</kwd><kwd>LINE-1</kwd><kwd>ORF1</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a CovidV2
| This area was generated with Dilib version V0.6.33. |  |