title: Herpes simplex virus type 1-induced FasL expression in human monocytic cells and its implications for cell death, viral replication, and immune evasion.
abstract: Herpes simplex virus type 1 (HSV-1) is a ubiquitously occurring pathogen that infects humans early in childhood. The virus persists as a latent infection in dorsal root ganglia, especially of the trigeminal nerve, and frequently becomes reactivated in humans under conditions of stress. Monocytic cells constitute an important component of the innate and adaptive immune responses. We show here for the first time that HSV-1 stimulates human FasL promoter and induces de novo expression of FasL on the surface of human monocytic cells, including monocytes and macrophages. This virus-induced FasL expression causes death of monocytic cells growing in suspension, but not in monolayers (e.g., macrophages). The addition of a broad-spectrum caspase inhibitor, as well as anti-FasL antibodies, reduced cell death but increased viral replication in the virus-infected cell cultures. We also show here for the first time that the virus-induced de novo expression of FasL on the cell surface acts as an immune evasion mechanism by causing the death of interacting human CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. Our study provides novel insights on FasL expression and cell death in HSV-infected human monocytic cells and their impact on interacting immune cells.
authors.affiliation: Laboratory of Innate Immunity, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iannello
authors.forename: Olfa
authors.initials: O
authors.lastname: Debbeche
authors.forename: Raoudha
authors.initials: R
authors.lastname: El Arabi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.forename: David
authors.initials: D
authors.lastname: Hamel
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Heveker
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death; D002460:Cell Line; D053222:Fas Ligand Protein / Q000096:biosynthesis*; D015870:Gene Expression; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D014779:Virus Replication
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein