Dengue virus infection induces autophagy: An in vivo study

Ying Ray Lee, Hsuan Yun Hu, Szu Han Kuo, Huan Yao Lei, Yee Shin Lin, Trai Ming Yeh, Ching Chuan Liu, Hsiao Sheng Liu

Research output: Contribution to journalArticle

48 Citations (Scopus)

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. Results and 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.

Original languageEnglish
Article number65
JournalJournal of biomedical science
Volume20
Issue number1
DOIs
Publication statusPublished - 2013 Sep 11

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Dengue Virus
Autophagy
Virus Diseases
Viruses
Virus Replication
Brain
IGF Type 2 Receptor
Viral Structural Proteins
Tissue
Inbred ICR Mouse
Membranes
Endosomes
Proteins
Cerebrum
Sirolimus
Mesencephalon
Transmission Electron Microscopy
Western Blotting
Staining and Labeling
Cells

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Lee, Ying Ray ; Hu, Hsuan Yun ; Kuo, Szu Han ; Lei, Huan Yao ; Lin, Yee Shin ; Yeh, Trai Ming ; Liu, Ching Chuan ; Liu, Hsiao Sheng. / Dengue virus infection induces autophagy : An in vivo study. In: Journal of biomedical science. 2013 ; Vol. 20, No. 1.
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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. Results and 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.",
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Dengue virus infection induces autophagy : An in vivo study. / Lee, Ying Ray; Hu, Hsuan Yun; Kuo, Szu Han; Lei, Huan Yao; Lin, Yee Shin; Yeh, Trai Ming; Liu, Ching Chuan; Liu, Hsiao Sheng.

In: Journal of biomedical science, Vol. 20, No. 1, 65, 11.09.2013.

Research output: Contribution to journalArticle

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AU - Kuo, Szu Han

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AU - Lin, Yee Shin

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AU - Liu, Ching Chuan

AU - Liu, Hsiao Sheng

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N2 - 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. Results and 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.

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