title: Human cytomegalovirus suppresses Fas expression and function.
abstract: Human cytomegalovirus (HCMV) is known to evade extrinsic pro-apoptotic pathways not only by downregulating cell surface expression of the death receptors TNFR1, TRAIL receptor 1 (TNFRSF10A) and TRAIL receptor 2 (TNFRSF10B), but also by impeding downstream signalling events. Fas (CD95/APO-1/TNFRSF6) also plays a prominent role in apoptotic clearance of virus-infected cells, so its fate in HCMV-infected cells needs to be addressed. Here, we show that cell surface expression of Fas was suppressed in HCMV-infected fibroblasts from 24 h onwards through the late phase of productive infection, and was dependent on de novo virus-encoded gene expression but not virus DNA replication. Significant levels of the fully glycosylated (endoglycosidase-H-resistant) Fas were retained within HCMV-infected cells throughout the infection within intracellular membranous structures. HCMV infection provided cells with a high level of protection against Fas-mediated apoptosis. Downregulation of Fas was observed with HCMV strains AD169, FIX, Merlin and TB40.
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Seirafian
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Virginie
authors.initials: V
authors.lastname: Prod'homme
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sugrue
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: James
authors.initials: J
authors.lastname: Davies
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Ceri
authors.initials: C
authors.lastname: Fielding
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Tomasec
authors.affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Gavin W G
authors.initials: GWG
authors.lastname: Wilkinson
mesh_terms: D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: C491901:FAS protein, human; D019014:fas Receptor