Abstract:
UNLABELLED:The latent HIV reservoir is a major impediment to curing HIV infection. The contribution of CD4(+) T cell activation status to the establishment and maintenance of the latent reservoir was investigated by enumerating viral DNA components in a cohort of 12 individuals commencing antiretroviral therapy (ART) containing raltegravir, an integrase inhibitor. Prior to ART, the levels of total HIV DNA were similar across HLA-DR(+) and HLA-DR(-) (HLA-DR(±)) CD38(±) memory CD4(+) T cell phenotypes; episomal two-long terminal repeat (2-LTR) HIV DNA levels were higher in resting (HLA-DR(-) CD38(-)) cells, and this phenotype exhibited a significantly higher ratio of 2-LTR to integrated HIV DNA (P = 0.002). After 1 year of ART, there were no significant differences across each of the memory phenotypes of any HIV DNA component. The decay dynamics of integrated HIV DNA were slow within each subset, and integrated HIV DNA in the resting HLA-DR(-) CD38(-) subset per mm(3) of peripheral blood exhibited no significant decay (half-life of 25 years). Episomal 2-LTR HIV DNA decayed relative to integrated HIV DNA in resting cells with a half-life of 134 days. Surprisingly, from week 12 on, the decay rates of both total and episomal HIV DNA were lower in activated CD38(+) cells. By weeks 24 and 52, HIV RNA levels in plasma were most significantly correlated with the numbers of resting cells containing integrated HIV DNA. On the other hand, total HIV DNA levels in all subsets were significantly correlated with the numbers of HLA-DR(+) CD38(-) cells containing integrated HIV DNA. These results provide insights into the interrelatedness of cell activation and reservoir maintenance, with implications for the design of therapeutic strategies targeting HIV persistence. IMPORTANCE:It is generally believed that HIV is not cleared by extensive antiretroviral therapy (ART) due to the difficulty in eradicating the latent reservoir in resting CD4(+) T cells. New therapies that attempt to activate this reservoir so that immune or viral cytopathic mechanisms can remove those infected cells are currently being investigated. However, results obtained in this research indicate that activation, at least on some level, already occurs within this reservoir. Furthermore, we are the first to describe the dynamics of different HIV DNA species in resting and activated memory CD4+ T cell subsets that point to the role different levels of activation play in maintaining the HIV reservoir.
journal_name
J Viroljournal_title
Journal of virologyauthors
Murray JM,Zaunders JJ,McBride KL,Xu Y,Bailey M,Suzuki K,Cooper DA,Emery S,Kelleher AD,Koelsch KK,PINT Study Team.doi
10.1128/JVI.03331-13subject
Has Abstractpub_date
2014-03-01 00:00:00pages
3516-26issue
6eissn
0022-538Xissn
1098-5514pii
JVI.03331-13journal_volume
88pub_type
杂志文章abstract::Broad, multispecific CD4(+) and CD8(+) T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of ...
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.8.3635-3642.1990
更新日期:1990-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.64.5.2360-2368.1990
更新日期:1990-05-01 00:00:00
abstract:UNLABELLED:Phosphoinositides and phosphoinositide binding proteins play a critical role in membrane and protein trafficking in eukaryotes. Their critical role in replication of cytoplasmic viruses has just begun to be understood. Poxviruses, a family of large cytoplasmic DNA viruses, rely on the intracellular membranes...
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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.68.3.1782-1789.1994
更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.64.5.2041-2046.1990
更新日期:1990-05-01 00:00:00
abstract::The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cyste...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4546-4550.1992
更新日期:1992-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1988-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.1.379-384.1986
更新日期:1986-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jvi.74.3.1101-1113.2000
更新日期:2000-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11754-11766.2003
更新日期:2003-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.19.12332-12341.2005
更新日期:2005-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.3.1202-1207.1991
更新日期:1991-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.2.1546-1554.1999
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.64.11.5640-5644.1990
更新日期:1990-11-01 00:00:00
abstract:UNLABELLED:Bean pod mottle virus (BPMV) is a bipartite, positive-sense (+) RNA plant virus in the Secoviridae family. Its RNA1 encodes proteins required for genome replication, whereas RNA2 primarily encodes proteins needed for virion assembly and cell-to-cell movement. However, the function of a 58-kDa protein (P58) e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03301-13
更新日期:2014-03-01 00:00:00
abstract::Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that conval...
journal_title:Journal of virology
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journal_title:Journal of virology
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更新日期:1998-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.12.6461-6467.1991
更新日期:1991-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01702-15
更新日期:2015-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06967-11
更新日期:2012-04-01 00:00:00
abstract::Members of the Paramyxovirinae subfamily rely on the concerted action of two envelope glycoprotein complexes, attachment protein H and the fusion (F) protein oligomer, to achieve membrane fusion for viral entry. Despite advances in X-ray information, the organization of the physiological attachment (H) oligomer in fun...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01222-10
更新日期:2010-12-01 00:00:00
abstract::The small and middle T (tumor) antigens of polyomavirus have been shown previously to associate with the 36-kDa catalytic subunit and the 63-kDa regulatory subunit of protein phosphatase type 2A, apparently substituting for a normal third 55-kDa regulatory subunit (D.C. Pallas, L.K. Shahrik, B.L. Martin, S. Jaspers, T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.886-893.1992
更新日期:1992-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.2.99-108.1970
更新日期:1970-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00137-17
更新日期:2017-04-28 00:00:00
abstract::Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections lead to rapid depletion of CD4(+) T cells from gut-associated lymphoid tissue (GALT). Although the administration of antiretroviral therapy (ART) has been shown to increase CD4(+) T-cell levels in the peripheral blood in both SIV and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.5.2709-2719.2005
更新日期:2005-03-01 00:00:00
abstract::Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00056-17
更新日期:2017-05-26 00:00:00
abstract:UNLABELLED:The discovery that measles virus (MV) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize its rapid spread in the airway epithelium. We show here that in well-differentiated primary cultures of airway epithelial cells from human donor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00821-15
更新日期:2015-07-01 00:00:00