title: HIV-1 Vpr activates both canonical and noncanonical NF-κB pathway by enhancing the phosphorylation of IKKα/β.
abstract: The human immunodeficiency virus type I (HIV-1) Vpr plays an essential role in viral replication. A number of studies have reported that Vpr modulates the nuclear factor-κB (NF-κB) pathway. Yet, the reported effects of Vpr on NF-κB signaling are controversial. In this study, we investigate the interplay between Vpr and NF-κB pathway. We discover that HIV-1 infection elevates the phosphorylation of IκBα and p100, and that this increase is greatly reduced when a Vpr-negative HIV-1 is used for infection. Our data further show that Vpr regulates the activity of IKKα/β through interactions. In addition, Vpr modulates the phosphorylation of p65 and p100, suggesting that Vpr activates both canonical and noncanonical NF-κB pathway. Knock down of endogenous IKKα/β result in a decrease in Vpr-mediated NF-κB and HIV-1 LTR activation. Given that Vpr is present in HIV-1 particles, our data suggest that Vpr activates the NF-κB pathway immediately after HIV-1 entry.
authors: Key Laboratory of Molecular Microbiology and Biotechnology, Ministry of Education and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Ruikang
authors: R
authors: Liu
authors: Juan
authors: J
authors: Tan
authors: Yongquan
authors: Y
authors: Lin
authors: Rui
authors: R
authors: Jia
authors: Wei
authors: W
authors: Yang
authors: Chen
authors: C
authors: Liang
authors: Yunqi
authors: Y
authors: Geng
authors: Wentao
authors: W
authors: Qiao
mesh_terms: D002460:Cell Line; D004720:Endonucleases; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D051550:I-kappa B Kinase; D004720:Endonucleases; C095221:SND1 protein, human