title: Gamma interferon-inducible lysosomal thioreductase (GILT) ablation renders mouse fibroblasts sensitive to dengue virus replication.
abstract: Dengue viruses (DENV), members of mosquito-borne Flaviviruses, are human pathogens of global significance. The virus enters the host cell through endocytosis and uncoating subsequent to a low pH-triggered conformational change of E protein in endosomes. The endosomes are active in antigen processing and the key enzyme involved is the gamma interferon-inducible lysosomal thiol reductase (GILT). Here, we sought to address the role of GILT in DENV2 entry using fibroblasts from wild type (WT) and GILT knockout (GILT(-/-)) mice (MFs) with defective antigen processing. Our results obtained using DENV2 infectious and Renilla luciferase reporter replicon RNAs show that WT MFs are relatively resistant and GILT(-/-) MFs are susceptible to DENV2 translation and replication. We show that DENV2 infection of WT MEFs induced autophagy based on an increased LC3-II/LC3-I ratio that is further enhanced in GILT(-/-) cells. The increased susceptibility of DENV2 infection in the GILT(-/-)MFs strongly correlates with increased autophagy.
authors: Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Tadahisa
authors: T
authors: Teramoto
authors: Hao-sen
authors: HS
authors: Chiang
authors: Ratree
authors: R
authors: Takhampunya
authors: Mark
authors: M
authors: Manzano
authors: Radhakrishnan
authors: R
authors: Padmanabhan
authors: Maja
authors: M
authors: Maric
mesh_terms: D000818:Animals; D001343:Autophagy; D003716:Dengue Virus / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology*; D017930:Genes, Reporter; D054884:Host-Pathogen Interactions; D008156:Luciferases / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013194:Staining and Labeling; D053586:Virus Internalization
chemical_list: D010088:Oxidoreductases; D008156:Luciferases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors