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 language | English |
|---|---|
| Article number | 65 |
| Journal | Journal of biomedical science |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Sep 11 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Pharmacology (medical)
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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 journal › Article
TY - JOUR
T1 - Dengue virus infection induces autophagy
T2 - An in vivo study
AU - Lee, Ying Ray
AU - Hu, Hsuan Yun
AU - Kuo, Szu Han
AU - Lei, Huan Yao
AU - Lin, Yee Shin
AU - Yeh, Trai Ming
AU - Liu, Ching Chuan
AU - Liu, Hsiao Sheng
PY - 2013/9/11
Y1 - 2013/9/11
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84883548577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883548577&partnerID=8YFLogxK
U2 - 10.1186/1423-0127-20-65
DO - 10.1186/1423-0127-20-65
M3 - Article
C2 - 24011333
AN - SCOPUS:84883548577
VL - 20
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
SN - 1021-7770
IS - 1
M1 - 65
ER -