title: Genome-wide transcriptional profiling reveals that HIV-1 Vpr differentially regulates interferon-stimulated genes in human monocyte-derived dendritic cells.
abstract: 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.
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan; International Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan.
authors.forename: Muhammad Atif
authors.initials: MA
authors.lastname: Zahoor
authors.affiliation: 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.
authors.forename: Guangai
authors.initials: G
authors.lastname: Xue
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sato
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan. Electronic address: aida@riken.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015894:Genome, Human; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D050835:Interferon Regulatory Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1
keywords: HIV-1 Vpr; Immune response; Interferon stimulation genes (ISGs); Microarray; Monocyte-derived dendritic cells; Recombinant adenoviral vector; Type I interferon