Abstract:
:The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef is heavily targeted by CD8(+) T lymphocytes (CTLs) during acute infection and therefore is included in many candidate vaccines. We investigated whether CTL targeting of Nef during acute infection contributes to immune control by disrupting the function of Nef. The sequence and function of Nef in parallel with CTL responses were assessed longitudinally from peak viremia until the viremia set point in a cohort of six subjects with acute infection. All but one individual had a single founder strain. Nef-specific CTL responses were detected in all subjects and declined in magnitude over time. These responses were associated with mutations, but none of the mutations were detected in important functional motifs. Nef-mediated downregulation of CD4 and major histocompatibility complex (MHC) class I molecules was better preserved in acute infection than in chronic infection. Finally, Nef-specific CTL responses were not associated with a reduction in viremia from its acute-phase peak. Our results indicate that CTLs targeting Nef epitopes outside critical functional domains have little effect on the pathogenic functions of Nef, rendering these responses ineffective in acute infection. Importance: These data indicate that using the whole Nef protein as a vaccine immunogen likely allows immunodominance that leads to targeting of CTL responses that are rapidly escaped with little effect on Nef-mediated pathogenic functions. Pursuing vaccination approaches that can more precisely direct responses to vulnerable areas would maximize efficacy. Until vaccine-induced targeting can be optimized, other approaches, such as the use of Nef function inhibitors or the pursuit of immunotherapies such as T cell receptor gene therapy or adoptive transfer, may be more likely to result in successful control of viremia.
journal_name
J Viroljournal_title
Journal of virologyauthors
De La Cruz J,Vollbrecht T,Frohnen P,Ng HL,Daar ES,Yang OO,Lewis MJdoi
10.1128/JVI.00482-14subject
Has Abstractpub_date
2014-07-01 00:00:00pages
7881-92issue
14eissn
0022-538Xissn
1098-5514pii
JVI.00482-14journal_volume
88pub_type
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doi:10.1128/JVI.69.8.4656-4667.1995
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doi:10.1128/JVI.00097-07
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doi:10.1128/JVI.02249-07
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8384-8391.1998
更新日期:1998-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.363-368.1986
更新日期:1986-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.68.7.4196-4203.1994
更新日期:1994-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.4.578-585.1972
更新日期:1972-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01943-12
更新日期:2013-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.66.1.432-439.1992
更新日期:1992-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.1.114-128.1980
更新日期:1980-07-01 00:00:00
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journal_title:Journal of virology
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doi:10.1128/JVI.75.2.661-671.2001
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
doi:10.1128/JVI.44.3.932-938.1982
更新日期:1982-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.11.5430-5440.1990
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2425-2432.1994
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journal_title:Journal of virology
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journal_title:Journal of virology
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pub_type: 杂志文章
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更新日期:2000-05-01 00:00:00
abstract:UNLABELLED:Antibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against R...
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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:2004-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.5.646-650.1971
更新日期:1971-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2182-2191.1987
更新日期:1987-07-01 00:00:00
abstract::The copy choice model for the generation of defective interfering (DI) particles of vesicular stomatitis virus suggests that during replication the polymerase prematurely terminates, moves with the nascent daughter strand to another site on the same or a different template molecule, and resumes elongation of the nasce...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.2.515-521.1984
更新日期:1984-08-01 00:00:00
abstract::High-risk human papillomaviruses (HPVs), including HPV-16 and HPV-18, are the causative agents of cervical carcinomas and are linked to several other tumors of the anogenital and oropharyngeal regions. The majority of HPV-induced tumors contain integrated copies of the normally episomal HPV genome that invariably reta...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2014-10-01 00:00:00