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Multivesicular body sorting and the exosomal pathway are required for the release of rat hepatitis E virus from infected cells.
- Source :
-
Virus research [Virus Res] 2020 Mar; Vol. 278, pp. 197868. Date of Electronic Publication: 2020 Jan 18. - Publication Year :
- 2020
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Abstract
- Recent reports have shown that rat hepatitis E virus (HEV) is capable of infecting humans. We also successfully propagated rat HEV into human PLC/PRF/5 cells, raising the possibility of a similar mechanism shared by human HEV and rat HEV. Rat HEV has the proline-rich sequence, PxYPMP, in the open reading frame 3 (ORF3) protein that is indispensable for its release. However, the release mechanism remains unclear. The overexpression of dominant-negative (DN) mutant of vacuolar protein sorting (Vps)4A or Vps4B decreased rat HEV release to 23.9 % and 18.0 %, respectively. The release of rat HEV was decreased to 8.3 % in tumor susceptibility gene 101 (Tsg101)-depleted cells and to 31.5 % in apoptosis-linked gene 2-interacting protein X (Alix)-depleted cells. Although rat HEV ORF3 protein did not bind to Tsg101, we found a 90-kDa protein capable of binding to wild-type rat HEV ORF3 protein but not to ORF3 mutant with proline to leucine mutations in the PxYPMP motif. Rat HEV release was also decreased in Ras-associated binding 27A (Rab27A)- or hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-depleted cells (to 20.1 % and 18.5 %, respectively). In addition, the extracellular rat HEV levels in the infected PLC/PRF/5 cells were increased after treatment with Bafilomycin A1 and decreased after treatment with GW4869. These results indicate that rat HEV utilizes multivesicular body (MVB) sorting for its release and that the exosomal pathway is required for rat HEV egress. A host protein alternative to Tsg101 that can bind to rat HEV ORF3 should be explored in further study.<br />Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Endosomal Sorting Complexes Required for Transport genetics
Endosomal Sorting Complexes Required for Transport metabolism
Humans
Protein Transport
Rats
Transcription Factors genetics
Transcription Factors metabolism
Viral Proteins metabolism
Virus Replication
Exosome Multienzyme Ribonuclease Complex physiology
Hepatitis E virus physiology
Multivesicular Bodies physiology
Multivesicular Bodies virology
Virus Release
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7492
- Volume :
- 278
- Database :
- MEDLINE
- Journal :
- Virus research
- Publication Type :
- Academic Journal
- Accession number :
- 31962066
- Full Text :
- https://doi.org/10.1016/j.virusres.2020.197868