title: Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.
abstract: During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. Such degradation subsequently results in the inhibition of type I interferon production in the infected cell. Our data demonstrate a mechanism by which cGAS senses cellular damage upon DENV infection.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aguirre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Luthra
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Sanchez-Aparicio
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Maestre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Jenish
authors.initials: J
authors.lastname: Patel
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Francise
authors.initials: F
authors.lastname: Lamothe
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Fredericks
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Shashank
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pintado-Silva
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Webb
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Dabeiba
authors.initials: D
authors.lastname: Bernal-Rubio
authors.affiliation: Tisch Cancer Institute, Division of Hematology and Medical Oncology, Department of Medicine, Department of Pathology and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Solovyov
authors.affiliation: Tisch Cancer Institute, Division of Hematology and Medical Oncology, Department of Medicine, Department of Pathology and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Greenbaum
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Lubbertus C F
authors.initials: LC
authors.lastname: Mulder
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000821:virology; D003715:Dengue / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D004272:DNA, Mitochondrial; D007370:Interferon Type I; D008565:Membrane Proteins; D009713:Nucleotidyltransferases; D017361:Viral Nonstructural Proteins; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase