Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1

Retrovirology

Yukihito Ishizaka⁵  Tadashi Okamura³  Shinichi Oka⁹  Motoko Yanagita²  Taku Iguchi²  Masanori Baba⁷  Hiroyuki Gatanaga⁹  Junko Tanuma⁹  Shotaro Hagiwara⁶  Shigeyuki Kano⁸  Shigeki Hoshino⁵  Taeko Dohi⁴  Takeshi Otsubo⁴  Yuki I Kawamura⁴  Akihiro Matsunaga⁵  Motohito Goto³  Mari Shimura⁵  Yoshikazu Saito⁵  Akihiro Doi¹  Masato Tamura⁵  Noriyuki Okudaira¹  Kenta Iijima⁵ 

[1] Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba 305-8577, Japan;Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan;Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;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;Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;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;AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan

关键词: ORF1;    LINE-1;    Retrotransposition;    Blood;    Vpr;    HIV-1;   

Others  :  1209090
DOI  :  10.1186/1742-4690-10-83

 received in 2012-11-16, accepted in 2013-07-18,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Iijima et al.; licensee BioMed Central Ltd.

【 图 表 】

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