Virus Name | Dengue virus 2 |
Virus Short Name | DENV 2 |
Order | Unassigned |
Virus Family | Flaviviridae |
Virus Subfamily | N.A. |
Genus | Flavivirus |
Species | Dengue virus |
Host | Human, mammals, mosquitoes and ticks |
Cell Tropism | Phagocytes, hepatocytes |
Associated Disease | Dengue fever |
Mode of Transmission | Arthropod bite, mainly mosquitoes |
VIPR DB link | http://www.viprbrc.org/brc/home.spg?decorator=flavi |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae |
Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Flaviviridae |
Paper Title | Cellular vimentin regulates construction of dengue virus replication complexes through Interaction with NS4A Protein |
Author's Name | Catherine Su Hui Teo, Justin Jang Hann Chu |
Journal Name | JOURNAL OF VIROLOGY |
Pubmed ID | 24284321 |
Abstract | Dengue virus (DENV) interacts with host cellular factors to construct a more favorable environment for replication, and the in- terplay between DENV and the host cellular cytoskeleton may represent one of the potential antiviral targeting sites. However, the involvement of cellular vimentin intermediate filaments in DENV replication has been explored less. Here, we revealed the direct interaction between host cellular vimentin and DENV nonstructural protein 4A (NS4A), a known component of the viral replication complex (RC), during DENV infection using tandem affinity purification, coimmunoprecipitation, and scanning electron microscopy. Furthermore, the dynamics of vimentin-NS4A interaction were demonstrated by using confocal three-di- mensional (3D) reconstruction and proximity ligation assay. Most importantly, we report for the first time the discovery of the specific region of NS4A that interacts with vimentin lies within the first 50 amino acid residues at the cytosolic N-terminal do- main of NS4A (N50 region). Besides identifying vimentin-NS4A interaction, vimentin reorganization and phosphorylation by calcium calmodulin-dependent protein kinase II occurs during DENV infection, signifying that vimentin reorganization is im- portant in maintaining and supporting the DENV RCs. Interestingly, we found that gene silencing of vimentin by small interfer- ing RNA induced a significant alteration in the distribution of RCs in DENV-infected cells. This finding further supports the cru- cial role of intact vimentin scaffold in localizing and concentrating DENV RCs at the perinuclear site, thus facilitating efficient viral RNA replication. Collectively, our findings implicate the biological and functional significance of vimentin during DENV replication, as we propose that the association of DENV RCs with vimentin is mediated by DENV NS4A. |
Used Model | Huh-7 cells |
DOI | 10.1128/JVI.01249-13 |