title: Dengue virus infection induces autophagy: an in vivo study.
abstract: BACKGROUND
  We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated.
  
  
  CONCLUSIONS
  The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice.We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. a713@mail.ncku.edu.tw.
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
authors.forename: Hsuan-Yun
authors.initials: HY
authors.lastname: Hu
authors.forename: Szu-Han
authors.initials: SH
authors.lastname: Kuo
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000494:pharmacology; D001343:Autophagy; D015153:Blotting, Western; D003715:Dengue / Q000503:physiopathology* / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007120:Immunochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D020123:Sirolimus / Q000494:pharmacology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000963:Antimetabolites; D007166:Immunosuppressive Agents; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus