title: Identification of Interferon-Stimulated Genes with Antiretroviral Activity.
abstract: Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kane
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, New York, NY 10016 USA.
authors.forename: Trinity M
authors.initials: TM
authors.lastname: Zang
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Suzannah J
authors.initials: SJ
authors.lastname: Rihn
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Fengwen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tonya
authors.initials: T
authors.lastname: Kueck
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Mudathir
authors.initials: M
authors.lastname: Alim
authors.affiliation: Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schoggins
authors.affiliation: Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow G61 1QH, UK. Electronic address: sam.wilson@glasgow.ac.uk.
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Wilson
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10065, USA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, New York, NY 10016 USA. Electronic address: pbienias@adarc.org.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D015723:Gene Library; D005820:Genetic Testing; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D008253:Macaca mulatta; D012190:Retroviridae / Q000276:immunology* / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007372:Interferons; D044767:Ubiquitin-Protein Ligases