Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses.
Flaviviruses deliver their genome into the cell by fusing the viral lipid membrane to an endosomal membrane. The sequence and kinetics of the steps required for nucleocapsid delivery into the cytoplasm remain unclear. Here we dissect the cell entry pathway of virions and virus-like particles from tw...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3764215?pdf=render |
| _version_ | 1818452279833919488 |
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| author | Adel M Nour Yue Li Joseph Wolenski Yorgo Modis |
| author_facet | Adel M Nour Yue Li Joseph Wolenski Yorgo Modis |
| author_sort | Adel M Nour |
| collection | DOAJ |
| description | Flaviviruses deliver their genome into the cell by fusing the viral lipid membrane to an endosomal membrane. The sequence and kinetics of the steps required for nucleocapsid delivery into the cytoplasm remain unclear. Here we dissect the cell entry pathway of virions and virus-like particles from two flaviviruses using single-particle tracking in live cells, a biochemical membrane fusion assay and virus infectivity assays. We show that the virus particles fuse with a small endosomal compartment in which the nucleocapsid remains trapped for several minutes. Endosomal maturation inhibitors inhibit infectivity but not membrane fusion. We propose a flavivirus cell entry mechanism in which the virus particles fuse preferentially with small endosomal carrier vesicles and depend on back-fusion of the vesicles with the late endosomal membrane to deliver the nucleocapsid into the cytoplasm. Virus entry modulates intracellular calcium release and phosphatidylinositol-3-phosphate kinase signaling. Moreover, the broadly cross-reactive therapeutic antibody scFv11 binds to virus-like particles and inhibits fusion. |
| first_indexed | 2024-12-14T21:20:34Z |
| format | Article |
| id | doaj.art-6030489fcb1646ff8baa00071cf6a27e |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-14T21:20:34Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6030489fcb1646ff8baa00071cf6a27e2022-12-21T22:46:57ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0199e100358510.1371/journal.ppat.1003585Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses.Adel M NourYue LiJoseph WolenskiYorgo ModisFlaviviruses deliver their genome into the cell by fusing the viral lipid membrane to an endosomal membrane. The sequence and kinetics of the steps required for nucleocapsid delivery into the cytoplasm remain unclear. Here we dissect the cell entry pathway of virions and virus-like particles from two flaviviruses using single-particle tracking in live cells, a biochemical membrane fusion assay and virus infectivity assays. We show that the virus particles fuse with a small endosomal compartment in which the nucleocapsid remains trapped for several minutes. Endosomal maturation inhibitors inhibit infectivity but not membrane fusion. We propose a flavivirus cell entry mechanism in which the virus particles fuse preferentially with small endosomal carrier vesicles and depend on back-fusion of the vesicles with the late endosomal membrane to deliver the nucleocapsid into the cytoplasm. Virus entry modulates intracellular calcium release and phosphatidylinositol-3-phosphate kinase signaling. Moreover, the broadly cross-reactive therapeutic antibody scFv11 binds to virus-like particles and inhibits fusion.http://europepmc.org/articles/PMC3764215?pdf=render |
| spellingShingle | Adel M Nour Yue Li Joseph Wolenski Yorgo Modis Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. PLoS Pathogens |
| title | Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. |
| title_full | Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. |
| title_fullStr | Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. |
| title_full_unstemmed | Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. |
| title_short | Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. |
| title_sort | viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses |
| url | http://europepmc.org/articles/PMC3764215?pdf=render |
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