Reid et al. 2016 (PRJNA285961)
General Details
| Title | Ribosome profiling analysis of Dengue Virus |
|---|---|
| Organism | |
| Number of Samples | 70 |
| Release Date | 2015/06/05 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
|---|---|
Repository Details
| SRA | SRP059187 |
|---|---|
| ENA | SRP059187 |
| GEO | GSE69602 |
| BioProject | PRJNA285961 |
Publication
| Title | |
|---|---|
| Authors | Reid DW, Campos RK, Child JR, Zheng T, Chan KWK, Bradrick SS, Vasudevan SG, Garcia-Blanco MA, Nicchitta CV |
| Journal | Journal of virology |
| Publication Date | 2018 Apr 1 |
| Abstract | A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways. IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention. Copyright © 2018 American Society for Microbiology. |
| PMC | PMC5972907 |
| PMID | 29321322 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SRR2052911 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide |  |
 |
 |
 |
|
|
||
| SRR2052912 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052913 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052914 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052915 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052916 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052917 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052918 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052919 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052920 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052921 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052922 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052923 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052924 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052925 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052926 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052927 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052928 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052929 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052930 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052931 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052932 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052933 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052934 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052935 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052936 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052937 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052938 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052939 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052940 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052941 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052942 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052943 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052944 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052945 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052946 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052947 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052948 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052949 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052950 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052951 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052952 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052953 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052954 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052955 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052956 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052957 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052958 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052983 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052984 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052985 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052986 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052987 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052988 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052989 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052990 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052991 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052992 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052993 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052994 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052995 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052996 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052997 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052998 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2052999 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2053000 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2053001 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2053002 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2053003 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| SRR2053004 | PRJNA285961 | Homo sapiens | Huh7 | Ribo-Seq | Cycloheximide | |
|
|
|
|
|
||
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
ⓘ For more Information on the columns shown here see: About