Abstract:
:We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with a focus on human immunodeficiency virus type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in the active site of FIV PR with structurally equivalent residues of HIV-1 PR dramatically altered the specificity of the mutant PRs in in vitro analyses. Here, we have expanded these studies to analyze the specificity changes in each mutant FIV PR expressed in the context of the natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared in which 4 to 12 HIV-1-equivalent substitutions were made in FIV PR, and cleavage of each Gag-Pol polyprotein was then assessed in pseudovirions from transduced cells. The findings demonstrated that, as with in vitro analyses, inhibitor specificities of the mutants showed increased HIV-1 PR character when analyzed against the natural substrate. In addition, all of the mutant PRs still processed the FIV polyprotein but the apparent order of processing was altered relative to that observed with wild-type FIV PR. Given the importance of the order in which Gag-Pol is processed, these findings likely explain the failure to produce infectious FIVs bearing these mutations.
journal_name
J Viroljournal_title
Journal of virologyauthors
Lin YC,Brik A,de Parseval A,Tam K,Torbett BE,Wong CH,Elder JHdoi
10.1128/JVI.00374-06subject
Has Abstractpub_date
2006-08-01 00:00:00pages
7832-43issue
16eissn
0022-538Xissn
1098-5514pii
80/16/7832journal_volume
80pub_type
杂志文章abstract::Poliovirus mutants in neutralizing antigenic site 3B were constructed by replacing the glutamic acid residue at amino acid 74 of capsid protein VP2 (VP2074E), using site-specific mutagenesis methods. All viable mutants display small-plaque phenotypes. Characterization of these mutants indicates that capsid assembly is...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.3.1641-1648.1992
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00376-14
更新日期:2014-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1377-1388.1995
更新日期:1995-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.11.7965-7973.1996
更新日期:1996-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.2.799-804.1979
更新日期:1979-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03469-12
更新日期:2013-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.6.3830-3840.1994
更新日期:1994-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2117-2125.1990
更新日期:1990-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6821-6830.1999
更新日期:1999-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02263-13
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.3.758-776.1981
更新日期:1981-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.6.3104-3107.1990
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.70.6.3753-3762.1996
更新日期:1996-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.17.8702-8709.2002
更新日期:2002-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7187-7195.1995
更新日期:1995-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.23.14606-14613.2005
更新日期:2005-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.7.3898-3912.2003
更新日期:2003-04-01 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
doi:10.1128/JVI.9.4.710-713.1972
更新日期:1972-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.3.781-790.1985
更新日期:1985-06-01 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:2011-01-01 00:00:00
abstract::The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2014-05-01 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:2014-01-01 00:00:00
abstract::Human immunodeficiency virus type 1 Tat exerts prominent angiogenic effects which may lead to a variety of vasculopathic conditions in AIDS patients. Because endothelial cells undergo prominent cytoskeletal rearrangement during angiogenesis, we investigated the specific effects of Tat on the endothelial cell actin cyt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.2.779-789.2004
更新日期:2004-01-01 00:00:00
abstract::The Gag-Pol polyprotein of human immunodeficiency virus type 1 (HIV-1) is not required for efficient viral particle production. However, premature termination codons in pol, particularly in the integrase (IN)-coding region, can markedly impair HIV-1 particle formation, apparently due to the premature activation of the...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2011-04-01 00:00:00
abstract::We report here the complete genomic sequence of the duck Tembusu virus (DTMUV) WJ-1 strain, isolated from Muscovy ducks. This is the first complete genome sequence of DTMUV reported in southern China. Compared with the other strains (TA, GH-2, YY5, and ZJ-407) that were previously found in eastern China, WJ-1 bears a ...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2012-12-01 00:00:00
abstract::Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent transcriptional activator of viral immediate-early (IE) genes. The VP16 activation domain can recruit various transcriptional coactivators to target gene promoters. However, the role of transcriptional coactivators in HSV-1 IE gene expression ...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2009-04-01 00:00:00
abstract::Rio Bravo virus (RBV) is a member of the family Flaviviridae, genus Flavivirus. It belongs to a group of viruses in the genus with no known vector. In this report, we analyze the complete genome of the prototype RBV, strain M64. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00331-12
更新日期:2012-04-01 00:00:00