Dhillon, P and Durga Rao, C (2018) Rotavirus induces formation of remodeled stress granules and P bodies and their sequestration in viroplasms to promote progeny virus production. In: Journal of Virology, 92 (24).
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Abstract
Rotavirus replicates in unique virus-induced cytoplasmic inclusion bodies called viroplasms (VMs), the composition and structure of which have yet to be understood. Based on the analysis of a few proteins, earlier studies reported that rotavirus infection inhibits stress granule (SG) formation and disrupts P bodies (PBs). However, the recent demonstration that rotavirus infection induces cytoplasmic relocalization and colocalization with VMs of several nuclear hnRNPs and AU-rich element-binding proteins (ARE-BPs), which are known components of SGs and PBs, suggested the possibility of rotavirus-induced remodeling of SGs and PBs, prompting us to analyze a large number of the SG and PB components to understand the status of SGs and PBs in rotavirus-infected cells. Here we demonstrate that rotavirus infection induces molecular triage by selective exclusion of a few proteins of SGs (G3BP1 and ZBP1) and PBs (DDX6, EDC4, and Pan3) and sequestration of the remodeled/atypical cellular organelles, containing the majority of their components, in the VM. The punctate SG and PB structures are seen at about 4 h postinfection (hpi), coinciding with the appearance of small VMs, many of which fuse to form mature large VMs with progression of infection. By use of small interfering RNA (siRNA)mediated knockdown and/or ectopic overexpression, the majority of the SG and PB components, except for ADAR1, were observed to inhibit viral protein expression and virus growth. In conclusion, this study demonstrates that VMs are highly complex supramolecular structures and that rotavirus employs a novel strategy of sequestration in the VM and harnessing of the remodeled cellular RNA recycling bins to promote its growth. IMPORTANCE Rotavirus is known to replicate in specialized virus-induced cytoplasmic inclusion bodies called viroplasms (VMs), but the composition and structure of VMs are not yet understood. Here we demonstrate that rotavirus interferes with normal SG and PB assembly but promotes formation of atypical SG-PB structures by selective exclusion of a few components and employs a novel strategy of sequestration of the remodeled SG-PB granules in the VMs to promote virus growth by modulating their negative influence on virus infection. Rotavirus VMs appear to be complex supramolecular structures formed by the union of the triad of viral replication complexes and remodeled SGs and PBs, as well as other host factors, and designed to promote productive virus infection. These observations have implications for the planning of future research with the aim of understanding the structure of the VM, the mechanism of morphogenesis of the virus, and the detailed roles of host proteins in rotavirus biology. Copyright © 2018 American Society for Microbiology. All Rights Reserved.
| Item Type: | Journal Article |
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| Publication: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | cell protein; DDX6 protein; EDC4 protein; G3BP1 protein; Pan3 protein; small interfering RNA; unclassified drug; viral protein; ZBP1 protein; heterogeneous nuclear ribonucleoprotein; RNA binding protein, animal cell; Article; cell body; cell count; cell granule; cell inclusion; cell organelle; cell structure; cell transformation; controlled study; disease course; gene knockdown; gene overexpression; human; human cell; molecular biology; nonhuman; priority journal; progeny; protein expression; Rotavirus; Rotavirus infection; stress granule; virogenesis; viroplasm; virus cell interaction; animal; cell line; Chlorocebus aethiops; HEK293 cell line; metabolism; physiology; Rotavirus; virology; virus inclusion; virus replication, Animals; Cell Line; Cercopithecus aethiops; HEK293 Cells; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Inclusion Bodies, Viral; RNA-Binding Proteins; Rotavirus; Rotavirus Infections; Virus Replication |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 23 Aug 2022 06:06 |
| Last Modified: | 23 Aug 2022 06:06 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76192 |
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