PMID- 26116899 OWN - NLM STAT- MEDLINE DCOM- 20160525 LR - 20150813 IS - 1872-7492 (Electronic) IS - 0168-1702 (Linking) VI - 208 DP - 2015 Oct 2 TI - Genome-wide transcriptional profiling reveals that HIV-1 Vpr differentially regulates interferon-stimulated genes in human monocyte-derived dendritic cells. PG - 156-63 LID - S0168-1702(15)00282-8 [pii] LID - 10.1016/j.virusres.2015.06.017 [doi] AB - Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that directly link the innate and adaptive immune responses. HIV-1 infection of DCs leads to a diverse array of changes in gene expression and play a major role in dissemination of the virus into T-cells. Although HIV-1 Vpr is a pleiotropic protein involved in HIV-1 replication and pathogenesis, its exact role in APCs such as DCs remains elusive. In this study, utilizing a microarray-based systemic biology approach, we found that HIV-1 Vpr differentially regulates (fold change >2.0) more than 200 genes, primarily those involved in the immune response and innate immune response including type I interferon signaling pathway. The differential expression profiles of select genes involved in innate immune responses (interferon-stimulated genes [ISGs]), including MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, and TNFSF10, were validated by real-time quantitative PCR; the results were consistent with the microarray data. Taken together, our findings are the first to demonstrate that HIV-1 Vpr induces ISGs and activates the type I IFN signaling pathway in human DCs, and provide insights into the role of Vpr in HIV-1 pathogenesis. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Zahoor, Muhammad Atif AU - Zahoor MA AD - Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan; International Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan. FAU - Xue, Guangai AU - Xue G AD - Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan; International Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan; Japanese Foundation of AIDS Prevention, Tokyo, Japan. FAU - Sato, Hirotaka AU - Sato H AD - Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan. FAU - Aida, Yoko AU - Aida Y AD - Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan. Electronic address: aida@riken.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150625 PL - Netherlands TA - Virus Res JT - Virus research JID - 8410979 RN - 0 (Interferon Regulatory Factors) RN - 0 (vpr Gene Products, Human Immunodeficiency Virus) RN - 0 (vpr protein, Human immunodeficiency virus 1) SB - IM MH - Dendritic Cells/cytology/*immunology MH - Genome, Human MH - HIV Infections/*genetics/immunology/virology MH - HIV-1/genetics/*metabolism MH - Host-Pathogen Interactions MH - Humans MH - Immunity, Innate MH - Interferon Regulatory Factors/*genetics/immunology MH - Monocytes/cytology/*immunology MH - vpr Gene Products, Human Immunodeficiency Virus/genetics/*metabolism OTO - NOTNLM OT - HIV-1 Vpr OT - Immune response OT - Interferon stimulation genes (ISGs) OT - Microarray OT - Monocyte-derived dendritic cells OT - Recombinant adenoviral vector OT - Type I interferon EDAT- 2015/06/28 06:00 MHDA- 2016/05/26 06:00 CRDT- 2015/06/28 06:00 PHST- 2015/04/23 00:00 [received] PHST- 2015/06/17 00:00 [revised] PHST- 2015/06/17 00:00 [accepted] PHST- 2015/06/28 06:00 [entrez] PHST- 2015/06/28 06:00 [pubmed] PHST- 2016/05/26 06:00 [medline] AID - S0168-1702(15)00282-8 [pii] AID - 10.1016/j.virusres.2015.06.017 [doi] PST - ppublish SO - Virus Res. 2015 Oct 2;208:156-63. doi: 10.1016/j.virusres.2015.06.017. Epub 2015 Jun 25.