Abstract:
UNLABELLED:Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been associated with a loss of CD4(+) T helper cell function and with the accumulation of anergic NK cells. As several studies have suggested that cytokines produced by CD4(+) T cells are required to enhance NK cell function in various infection models, we hypothesized that reconstitution of HIV-1-specific CD4(+) T-cell responses by therapeutic immunization would restore NK cell activity in infected individuals. Using flow cytometry, we examined the function of CD4(+) T cells and NK cells in response to HIV-1 in subjects with treated chronic HIV-1 infection before and after immunization with an adjuvanted HIV-1 Gp120/NefTat subunit protein vaccine candidate provided by GlaxoSmithKline. Vaccination induced an increased expression of interleukin-2 (IL-2) by Gp120-specific CD4(+) T cells in response to HIV-1 peptides ex vivo, which was associated with enhanced production of gamma interferon (IFN-γ) by NK cells. Our data show that reconstitution of HIV-1-specific CD4(+) T-cell function by therapeutic immunization can enhance NK cell activity in HIV-1-infected individuals. IMPORTANCE:NK cells are effector cells of the innate immune system and are important in the control of viral infection. Recent studies have demonstrated the crucial role played by NK cells in controlling and/or limiting acquisition of HIV-1 infection. However, NK cell function is impaired during progressive HIV-1 infection. We recently showed that therapeutic immunization of treated HIV-1-infected individuals reconstituted strong T-cell responses, measured notably by their production of IL-2, a cytokine that can activate NK cells. The current study suggests that reconstitution of T-cell function by therapeutic vaccination can enhance NK cell activity in individuals with chronic HIV-1 infection. Our findings provide new insights into the interplay between adaptive and innate immune mechanisms involved in HIV-1 immunity and unveil opportunities to harness NK cell function in future therapeutic vaccine strategies to target HIV-1.
journal_name
J Viroljournal_title
Journal of virologyauthors
Jost S,Tomezsko PJ,Rands K,Toth I,Lichterfeld M,Gandhi RT,Altfeld Mdoi
10.1128/JVI.00924-14subject
Has Abstractpub_date
2014-08-01 00:00:00pages
8349-54issue
15eissn
0022-538Xissn
1098-5514pii
JVI.00924-14journal_volume
88pub_type
杂志文章abstract::The role of the T4 bacteriophage regA gene in stabilizing early mRNA was investigated by assaying the level of functional mRNA from eight prereplicative genes (56 [dCMP hydroxymethylase], cd [dCMP deaminase], 1 [deoxynucleotide kinase], rIIA, rIIB, 46 [DNA arrest], and 45) during extended infection of Escherichia coli...
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doi:10.1128/JVI.17.2.538-549.1976
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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
doi:10.1128/JVI.42.3.767-772.1982
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pub_type: 杂志文章
doi:10.1128/JVI.73.1.738-745.1999
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6496-6501.1992
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doi:10.1128/JVI.70.11.8234-8240.1996
更新日期:1996-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.63.7.3026-3033.1989
更新日期:1989-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1996-2001.2001
更新日期:2001-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.2.622-626.1980
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
doi:10.1128/JVI.12.6.1195-1203.1973
更新日期:1973-12-01 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.66.1.573-579.1992
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.59.3.676-683.1986
更新日期:1986-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.66.6.3776-3783.1992
更新日期:1992-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.7.5.646-650.1971
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journal_title:Journal of virology
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doi:10.1128/JVI.68.6.4092-4096.1994
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4588-4597.1993
更新日期:1993-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.6.1109-1117.1972
更新日期:1972-12-01 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:2006-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00293-12
更新日期:2012-08-01 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.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.73.6.5207-5213.1999
更新日期:1999-06-01 00:00:00
abstract:UNLABELLED:Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understandi...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-09-01 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