title: IFN-εprotects primary macrophages against HIV infection.
abstract: IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controlsChlamydia muridarumand herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+T cells or transformed cell lines unless activated CD4+T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε-mediated HIV inhibition through immune modulation has implications for prevention.
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.
authors.forename: Carley
authors.initials: C
authors.lastname: Tasker
authors.affiliation: Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Selvakumar
authors.initials: S
authors.lastname: Subbian
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Couret
authors.affiliation: Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: Levine
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.
authors.forename: Saleena
authors.initials: S
authors.lastname: Ghanny
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.
authors.forename: Patricia
authors.initials: P
authors.lastname: Soteropoulos
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.|Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Landau
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics and.|Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D011506:Proteins / Q000378:metabolism; D000076106:SAM Domain and HD Domain-Containing Protein 1 / Q000378:metabolism; D014779:Virus Replication
chemical_list: C524005:IFNE protein, human; D011506:Proteins; D007372:Interferons; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase