Abstract:
:Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.
journal_name
J Viroljournal_title
Journal of virologyauthors
Hoenen T,Shabman RS,Groseth A,Herwig A,Weber M,Schudt G,Dolnik O,Basler CF,Becker S,Feldmann Hdoi
10.1128/JVI.01525-12subject
Has Abstractpub_date
2012-11-01 00:00:00pages
11779-88issue
21eissn
0022-538Xissn
1098-5514pii
JVI.01525-12journal_volume
86pub_type
杂志文章abstract:UNLABELLED:Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been assoc...
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章,收录出版
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更新日期:2004-05-01 00:00:00
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更新日期:2016-04-14 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.6.3139-3143.1990
更新日期:1990-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2009-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2427-2433.1995
更新日期:1995-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1994-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01467-06
更新日期:2007-02-01 00:00:00