Induction of G2 arrest and binding to cyclophilin A are independent phenotypes of human immunodeficiency virus type 1 Vpr
Induction of G2 arrest and binding to cyclophilin A are independent phenotypes of human immunodeficiency virus type 1 Vpr
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DOI：
10.1128/jvi.80.8.3694-3700.2006
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Planelles, V
中科院分区：
文献类型：
--
作者：
Ardon, O;Zimmerman, ES;Planelles, V
亲环素A（CypA）是具有肽基脯氨酰顺反异构酶（PPIase）活性的细胞蛋白家族的成员。CypA是人类免疫缺陷病毒1型（HIV-1）蛋白R（Vpr）的生化稳定性和功能（特别是诱导G（2）停滞）所必需的。在本研究中，我们研究了Vpr-CypA相互作用对Vpr诱导的G（2）阻滞的作用。我们发现，Vpr coimmunoprecipitates与CypA，这种相互作用被破坏的Vpr的脯氨酸-35的取代，以及与CypA抑制剂环孢素A（CsA）孵育。令人惊讶的是，CypA的存在或其与Vpr的结合与Vpr诱导G（2）阻滞的能力无关。Vpr在CypA（-/-）细胞中的表达导致G（2）阻滞的诱导，其方式与CypA（+）细胞中的诱导方式难以区分。CsA可阻断CypA-Vpr结合，但对诱导G（2）阻滞或Vpr稳态水平无影响。鉴于这些结果，我们提出，与CypA的相互作用是独立的Vpr诱导细胞周期阻滞的能力。Vpr和CypA之间的相互作用很有趣，进一步的研究应该考察其对Vpr其他功能的潜在影响。
Cyclophilin A (CypA) is a member of a family of cellular proteins that share a peptidyl prolyl cis-trans isomerase (PPIase) activity. CypA was previously reported to be required for the biochemical stability and function (specifically, induction of G(2) arrest) of the human immunodeficiency virus type 1 (HIV-1) protein R (Vpr). In the present study, we examine the role of the Vpr-CypA interaction on Vpr-induced G(2) arrest. We find that Vpr coimmunoprecipitates with CypA and that this interaction is disrupted by substitution of proline-35 of Vpr as well as incubation with the CypA inhibitor cyclosporine A (CsA). Surprisingly, the presence of CypA or its binding to Vpr is dispensable for the ability of Vpr to induce G(2) arrest. Vpr expression in CypA(-/-) cells leads to induction of G(2) arrest in a manner that is indistinguishable from that in CypA(+) cells. CsA abolished CypA-Vpr binding but had no effect on induction of G(2) arrest or Vpr steady-state levels. In view of these results, we propose that the interaction with CypA is independent of the ability of Vpr to induce cell cycle arrest. The interaction between Vpr and CypA is intriguing, and further studies should examine its potential effects on other functions of Vpr.