Abstract:
:The HIV-1 Nef protein is known to be secreted, and our group has shown that Nef is secreted from nef-transfected and HIV-1-infected cells in small exosome-like vesicles (d. 40-100 nm). The role of secreted Nef remains to be fully characterized. Thus, it is important to characterize the nature of and the mechanisms regulating Nef secretion. We hypothesized that specific structural domains on the Nef protein interact with components of the endosomal trafficking machinery, sorting Nef into multivesicular bodies (MVB) and packaging it in exosome-like vesicles. To identify those domains, a series of mutants spanning the entire nef sequence were made and cloned into the expression vector pQB1, which expresses the mutants as Nef-GFP fusion proteins. These constructs were used in transient transfection assays to identify sequences necessary for secretion of the Nef-GFP fusion protein. N-terminal domains were identified as critical for Nef-induced vesicle secretion: (1) a basic cluster of four arginine residues (aa 17, 19, 21, 22), (2) the phosphofurin acidic cluster sequence (PACS; Glu62-65), and (3) a previously uncharacterized domain spanning amino acid residues 66-70 (VGFPV), which we named the secretion modification region (SMR). Additional amino acids P25, 29GVG31, and T44 were identified in HIV-1 Nef as regulating its secretion. These residues have not been associated with other reported Nef functions. The myristoylation domain, ubiquitination lysine residues, and the C-terminal portion of Nef (aa 71-206) had no effect on secretion. A minimal HIV-1 Nef sequence, comprising the identified motifs, was sufficient for Nef-induced vesicle secretion.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Ali SA,Huang MB,Campbell PE,Roth WW,Campbell T,Khan M,Newman G,Villinger F,Powell MD,Bond VCdoi
10.1089/aid.2009.0068subject
Has Abstractpub_date
2010-02-01 00:00:00pages
173-92issue
2eissn
0889-2229issn
1931-8405journal_volume
26pub_type
杂志文章abstract::In a set of 42 antiretroviral naive HIV-1 infected persons who were treated with either Zidovudine (AZT) monotherapy, or a combination of AZT + ddC (Zalcitabine) or AZT + ddI (Didanosine), the HIV-1 DNA load was measured by competitive polymerase chain reaction (PCR) and related to the HIV-1 RNA load in plasma, the CD...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1089/aid.1998.14.1053
更新日期:1998-08-10 00:00:00
abstract::HIV-1 transcripts are generated through a complex alternative splicing mechanism, resulting in the production of multiple RNAs coding for each viral protein. HIV-1 RNA splicing has been analyzed mostly in in vitro assays, and in vivo data are scarce. Here we analyze HIV-1 transcripts generated in peripheral blood mono...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0011
更新日期:2010-07-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200750006092
更新日期:2000-10-10 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922203763315687
更新日期:2003-03-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922204323087705
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1989.5.107
更新日期:1989-02-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1990.6.951
更新日期:1990-07-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0102
更新日期:2015-10-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.1057
更新日期:2005-12-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-08-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,评审
doi:10.1089/aid.1994.10.901
更新日期:1994-08-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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更新日期:2001-08-10 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1289
更新日期:2004-12-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.932
更新日期:2004-09-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1987.3.253
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0192
更新日期:2007-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1089/aid.2019.0179
更新日期:2020-03-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311600
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2015.0026
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abstract::Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP C(trough) over time, as well as the impact of NVP C(trough) concent...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.555
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.933
更新日期:1995-08-01 00:00:00
abstract::HIV infection is associated with qualitative and functional immune deficiencies. It has been shown that the in vitro infection of CD4+ cells with HIV was associated with sustained elevation of cAMP and cGMP. In the present report the role of cAMP on HIV replication in MT-4 cells was investigated. The MT-4 cells were i...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
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