Summary

Retrovirology. 2013 Aug 5;10:83. doi: 10.1186/1742-4690-10-83.

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.

日本語要旨:

HIV-1患者血清中にレトロトランスポジション誘導活性を検出し、この活性がウイルス蛋白質であるVprに対する単クローン抗体でキャンセルされることを証明した。また、組み換えVpr蛋白質をマウスに投与すると、腎臓組織の尿細管でレトロトランスポジションが誘導された。特に黒人においてHIV-1に伴う腎機能不全が発症することが知られており、Vprがそのリスク因子として機能する可能性が示唆された。

PMID:  23915234

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