title: Checks and balances between human cytomegalovirus replication and indoleamine-2,3-dioxygenase.
abstract: Despite a rigorous blockade of interferon-γ (IFN-γ) signalling in infected fibroblasts as a mechanism of immune evasion by human cytomegalovirus (HCMV), IFN-γ induced indoleamine-2,3-dioxygenase (IDO) has been proposed to represent the major antiviral restriction factor limiting HCMV replication in epithelial cells. Here we show that HCMV efficiently blocks transcription of IFN-γ-induced IDO mRNA both in infected fibroblasts and epithelial cells even in the presence of a preexisting IFN-induced antiviral state. This interference results in severe suppression of IDO bioactivity in HCMV-infected cells and restoration of vigorous HCMV replication. Depletion of IDO expression nonetheless substantially alleviated the antiviral impact of IFN-γ treatment in both cell types. These findings highlight the effectiveness of this IFN-γ induced effector gene in restricting HCMV productivity, but also the impact of viral counter-measures.
authors: Institute for Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany.
authors: Albert
authors: A
authors: Zimmermann
authors: Institute for Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany.
authors: Sebastian
authors: S
authors: Hauka
authors: Institute for Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany.
authors: Marco
authors: M
authors: Maywald
authors: Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen 45147, Germany.
authors: Vu Thuy Khanh
authors: VTK
authors: Le
authors: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany.
authors: Silvia K
authors: SK
authors: Schmidt
authors: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany.
authors: Walter
authors: W
authors: Däubener
authors: Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg 79104, Germany.
authors: Hartmut
authors: H
authors: Hengel
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D014779:Virus Replication
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma