Abstract:
:Gammaretroviruses, such as murine leukemia virus (MLV), are functionally distinguished from lentiviruses, such as human immunodeficiency virus, by their inability to infect nondividing cells. Attempts to engineer this property into MLV have been hindered by an incomplete understanding of early events in the viral life cycle. We utilized a transposon-based method to generate saturated peptide insertion libraries of MLV gag-pol variants with nuclear localization signals randomly incorporated throughout these overlapping genes. High-throughput selection of the libraries via iterative retroviral infection of nondividing cells led to the identification of a novel variant that successfully transduced growth-arrested cells. Vector packaging by cotransfection of the gag-pol.NLS variant with wild-type gag-pol produced high-titer virions capable of infecting neurons in vitro and in vivo. The capacity of mutant virions to transduce nondividing cells could help to elucidate incompletely understood mechanisms of the viral life cycle and greatly broaden the gene therapy applications of retroviral vectors. Furthermore, the ability to engineer key intracellular viral infection steps has potential implications for the understanding, design, and control of other post-entry events. Finally, this method of library generation and selection for a desired phenotype directly in a mammalian system can be readily expanded to address other challenges in protein engineering.
journal_name
J Viroljournal_title
Journal of virologyauthors
Yu JH,Schaffer DVdoi
10.1128/JVI.00615-06subject
Has Abstractpub_date
2006-09-01 00:00:00pages
8981-8issue
18eissn
0022-538Xissn
1098-5514pii
80/18/8981journal_volume
80pub_type
杂志文章abstract::Scrapie-associated fibrils (SAFs) are abnormal filamentous structures that are uniquely associated with unconventional slow virus diseases. The antigenic relationships of SAFs from animals infected with four biologically distinct scrapie strains were investigated by using antisera raised to purified SAF proteins. Rabb...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.59.3.676-683.1986
更新日期:1986-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.4.2083-2090.1993
更新日期:1993-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.1.300-301.1984
更新日期:1984-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01554-20
更新日期:2020-11-23 00:00:00
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journal_title:Journal of virology
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更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.56.3.969-977.1985
更新日期:1985-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.75.8.3811-3818.2001
更新日期:2001-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01764-18
更新日期:2019-02-05 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.73.2.1350-1361.1999
更新日期:1999-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03824-13
更新日期:2014-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.6.2895-2900.1990
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
doi:10.1128/JVI.01994-20
更新日期:2020-12-09 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.26.1.136-142.1978
更新日期:1978-04-01 00:00:00
abstract::Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8(+) T cells cr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00936-13
更新日期:2013-12-01 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:2015-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5882-5889.1994
更新日期:1994-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00020-15
更新日期:2015-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2254-2260.1991
更新日期:1991-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2429-2433.1993
更新日期:1993-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2033-2040.1990
更新日期:1990-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jvi.78.2.585-594.2004
更新日期:2004-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.3.492-500.1973
更新日期:1973-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1559-1568.2002
更新日期:2002-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.07046-11
更新日期:2012-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.1.26-35.2001
更新日期:2001-01-01 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:2007-09-01 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:2011-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8798-8807.1997
更新日期:1997-11-01 00:00:00
abstract::CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides a promising target for antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.2.579-588.2001
更新日期:2001-01-01 00:00:00
abstract::Prasinoviruses infecting unicellular green algae in the order Mamiellales (class Mamiellophyceae) are commonly found in coastal marine waters where their host species frequently abound. We tested 40 Ostreococcus tauri viruses on 13 independently isolated wild-type O. tauri strains, 4 wild-type O. lucimarinus strains, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.07221-11
更新日期:2012-04-01 00:00:00