RRC ID 44569
著者 Iijima K, Okudaira N, Tamura M, Doi A, Saito Y, Shimura M, Goto M, Matsunaga A, Kawamura YI, Otsubo T, Dohi T, Hoshino S, Kano S, Hagiwara S, Tanuma J, Gatanaga H, Baba M, Iguchi T, Yanagita M, Oka S, Okamura T, Ishizaka Y.
タイトル Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1.
ジャーナル Retrovirology
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.
巻・号 10
ページ 83
公開日 2013-8-5
DOI 10.1186/1742-4690-10-83
PII 1742-4690-10-83
PMID 23915234
PMC PMC3751050
MeSH Adult Animals Gene Products, vpr / blood* Gene Products, vpr / metabolism* HIV-1 / enzymology* Humans Long Interspersed Nucleotide Elements* Male Mice Mice, Transgenic Recombination, Genetic* Young Adult
IF 4.183
引用数 16
WOS 分野 VIROLOGY
リソース情報
ヒト・動物細胞 HuH-7(RCB1366) 293T(RCB2202)