Abstract:
:Propagation of the flavivirus tick-borne encephalitis virus in BHK-21 cells selected for mutations within the large surface glycoprotein E that increased the net positive charge of the protein. In the course of 16 independent experiments, 12 different protein E mutation patterns were identified. These were located in all three of the structural domains and distributed over almost the entire upper and lateral surface of protein E. The mutations resulted in the formation of local patches of predominantly positive surface charge. Recombinant viruses carrying some of these mutations in a defined genetic backbone showed heparan sulfate (HS)-dependent phenotypes, resulting in an increased specific infectivity and binding affinity for BHK-21 cells, small plaque formation in porcine kidney cells, and significant attenuation of neuroinvasiveness in adult mice. Our results corroborate the notion that the selection of attenuated HS binding mutants is a common and frequent phenomenon during the propagation of viruses in cell culture and suggest a major role for HS dependence in flavivirus attenuation. Recognition of this principle may be of practical value for designing attenuated flavivirus strains in the future.
journal_name
J Viroljournal_title
Journal of virologyauthors
Mandl CW,Kroschewski H,Allison SL,Kofler R,Holzmann H,Meixner T,Heinz FXdoi
10.1128/JVI.75.12.5627-5637.2001subject
Has Abstractpub_date
2001-06-01 00:00:00pages
5627-37issue
12eissn
0022-538Xissn
1098-5514journal_volume
75pub_type
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pub_type: 杂志文章
doi:10.1128/JVI.63.9.3837-3843.1989
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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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journal_title:Journal of virology
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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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pub_type: 杂志文章
doi:10.1128/JVI.67.4.1765-1771.1993
更新日期:1993-04-01 00:00:00
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journal_title:Journal of virology
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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
doi:10.1128/JVI.78.20.11439-11442.2004
更新日期:2004-10-01 00:00:00
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journal_title:Journal of virology
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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
doi:10.1128/JVI.73.12.10320-10328.1999
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1980-11-01 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:2002-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.13.6162-6167.2000
更新日期:2000-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.12.6271-6281.2004
更新日期:2004-06-01 00:00:00
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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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更新日期:1975-09-01 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:2006-01-01 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:2003-11-01 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:2011-11-01 00:00:00