title: HIV-1 Vpr induces interferon-stimulated genes in human monocyte-derived macrophages.
abstract: Macrophages act as reservoirs of human immunodeficiency virus type 1 (HIV-1) and play an important role in its transmission to other cells. HIV-1 Vpr is a multi-functional protein involved in HIV-1 replication and pathogenesis; however, its exact role in HIV-1-infected human macrophages remains poorly understood. In this study, we used a microarray approach to explore the effects of HIV-1 Vpr on the transcriptional profile of human monocyte-derived macrophages (MDMs). More than 500 genes, mainly those involved in the innate immune response, the type I interferon pathway, cytokine production, and signal transduction, were differentially regulated (fold change >2.0) after infection with a recombinant adenovirus expressing HIV-1 Vpr protein. The differential expression profiles of select interferon-stimulated genes (ISGs) and genes involved in the innate immune response, including STAT1, IRF7, MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, APOBEC3A, DDX58 (RIG-I), TNFSF10 (TRAIL), and RSAD2 (viperin) were confirmed by real-time quantitative PCR and were consistent with the microarray data. In addition, at the post-translational level, HIV-1 Vpr induced the phosphorylation of STAT1 at tyrosine 701 in human MDMs. These results demonstrate that HIV-1 Vpr leads to the induction of ISGs and expand the current understanding of the function of Vpr and its role in HIV-1 immune pathogenesis.
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan; Japanese Foundation of AIDS Prevention, Tokyo, Japan.
authors.forename: Muhammad Atif
authors.initials: MA
authors.lastname: Zahoor
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, 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, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sato
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan.
authors.forename: Shin-nosuke
authors.initials: SN
authors.lastname: Takeshima
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D007372:Interferons