title: Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1.
abstract: BACKGROUND
  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 in vivo 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Iijima
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okudaira
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Doi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Saito
authors.forename: Mari
authors.initials: M
authors.lastname: Shimura
authors.forename: Motohito
authors.initials: M
authors.lastname: Goto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Yuki I
authors.initials: YI
authors.lastname: Kawamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otsubo
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hoshino
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
authors.forename: Shotaro
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Taku
authors.initials: T
authors.lastname: Iguchi
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D000328:Adult; D000818:Animals; D016336:Gene Products, vpr / Q000097:blood* / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D055815:Young Adult
chemical_list: D016336:Gene Products, vpr
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