scholarly journals Paucity of HIV DNA Methylation in Latently Infected, Resting CD4+ T Cells from Infected Individuals Receiving Antiretroviral Therapy

2012 ◽  
Vol 86 (9) ◽  
pp. 5390-5392 ◽  
Author(s):  
J. Blazkova ◽  
D. Murray ◽  
J. S. Justement ◽  
E. K. Funk ◽  
A. K. Nelson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Hiv Dna ◽  
Latently Infected

scholarly journals Interleukin-7 promotes HIV persistence during antiretroviral therapy

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4321-4329 ◽  
Author(s):  
Claire Vandergeeten ◽  
Rémi Fromentin ◽  
Sandrina DaFonseca ◽  
Mariam B. Lawani ◽  
Irini Sereti ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Viral Latency ◽  
Absolute Number ◽  
Hiv Persistence ◽  
Hiv Dna ◽  
Interleukin 7 ◽  
Key Points ◽  
Latently Infected

Key Points IL-7 does not disrupt viral latency in highly pure resting latently infected CD4+ T cells from HIV-infected subjects receiving ART. IL-7 therapy leads to a 70% increase in the absolute number of circulating CD4+ T cells harboring integrated HIV DNA 4 weeks posttherapy.

scholarly journals Enrichment of the HIV reservoir in CD32+ CD4 T cells occurs early in blood and tissue

2017 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
John P Thornhill ◽  
Chansavath Phetsouphanh ◽  
Jodi Meyerowitz ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Immune Checkpoint ◽  
Cd4 T Cells ◽  
Treatment Interruption ◽  
Healthy Controls ◽  
Hiv Dna ◽  
Hla Dr ◽  
Latently Infected ◽  
Checkpoint Receptors

AbstractThe Fc receptor CD32 has been proposed as a marker for CD4 T cells latently infected with HIV. We demonstrate that enrichment for HIV DNA in CD32+ CD4 T cells can be found early in infection in both tissue and blood. However, we find no evidence for a correlation between CD32 expression on CD4 T cells and either HIV DNA levels or time to rebound viraemia following treatment interruption. CD32+ CD4 T cells have a more differentiated memory phenotype, and high levels of expression of immune checkpoint receptors PD-1, Tim-3 and TIGIT as well as the activation marker, HLA DR. There was no difference in the phenotype or frequency of CD32 expressing cells prior to or after the initiation of antiretroviral therapy, or compared with healthy controls, suggesting that preferential infection or survival, rather than up-regulation, may be responsible for the observed enrichment of proviral HIV DNA in CD32+ CD4 T cells.

scholarly journals Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy

AIDS ◽  
2016 ◽  
Vol 30 (10) ◽  
pp. 1511-1520 ◽  
Author(s):  
Gabriela Khoury ◽  
Jenny L. Anderson ◽  
Rémi Fromentin ◽  
Wendy Hartogenesis ◽  
Miranda Z. Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Hiv Dna ◽  
Memory Cd4 T Cells

scholarly journals Blind Uneven Proliferation of CD4+ T cells During Primary Infection Generates the Majority of the HIV Reservoir

2020 ◽  
Author(s):  
Florencia A. T. Boshier ◽  
Daniel B. Reeves ◽  
Elizabeth R. Duke ◽  
David A. Swan ◽  
Martin Prlic ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cellular Proliferation ◽  
Chromosomal Dna ◽  
Hiv Replication ◽  
Hiv Reservoir ◽  
Viral Spread ◽  
Hiv Dna ◽  
Latently Infected ◽  
Memory Cd4 T Cells

AbstractThe HIV reservoir is a population of 1-10 million anatomically dispersed, latently infected memory CD4+ T cells in which an HIV DNA molecule is quiescently integrated into human chromosomal DNA. When antiretroviral therapy (ART) is stopped and HIV replication initiates in one of these cells, systemic viral spread resumes, rekindling progression to AIDS. Therefore, HIV latency prevents cure. The HIV reservoir contains clones: identical HIV sequences that are integrated within identical human chromosomal DNA locations. The presence of these clones demonstrates that proliferation of CD4+ T cells sustains infection despite ART. The reservoir has a precise structure consisting of a small number of large clones and a large number of small clones. However, the mechanisms leading to this structure have not been identified. We developed a mathematical model that recapitulates the profound depletion and brisk recovery of CD4+ T cells, reservoir creation, and viral load trajectory during primary HIV infection. We extended the model to simulate stochastically individual HIV reservoir clones and identified that uneven proliferation among clones during recovery from CD4+ lymphopaenia is sufficient to explain the observed clonal reservoir distribution. We project that within one month of infection 75-95% of reservoir cells are generated from cellular proliferation rather than denovo viral infection. Recent detection of HIV infected clones during the first 5 weeks of infection support our model’s predictions.

scholarly journals Induction of HIV-1 Replication in Latently Infected CD4+ T Cells Using a Combination of Cytokines

1998 ◽  
Vol 188 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Tae-Wook Chun ◽  
Delphine Engel ◽  
Stephanie B. Mizell ◽  
Linda A. Ehler ◽  
Anthony S. Fauci
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Proinflammatory Cytokines ◽  
Cd4 T Cells ◽  
Lymphoid Tissues ◽  
Tnf Α ◽  
Latently Infected ◽  
Hiv 1

Although it has been demonstrated that certain cytokines, particularly proinflammatory cytokines, can enhance ongoing viral replication in peripheral blood mononuclear cells (PBMCs) of HIV-1–infected individuals, it is unclear what role these cytokines play in the induction of HIV-1 replication in latently infected, resting CD4+ T cells. This study demonstrates that the in vitro combination of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α together with the immunoregulatory cytokine IL-2 are potent inducers of viral replication in highly purified, latently infected, resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral therapy–naive as well as those who are receiving highly active antiretroviral therapy (HAART). Viral replication induced by this combination of cytokines was completely suppressed in the presence of HAART in vitro. Given that an array of cytokines, including IL-6, TNF-α, and IL-2, are copiously expressed in the microenvironment of the lymphoid tissues, which harbor the latent viral reservoirs, induction of HIV by this combination of cytokines may in part explain the commonly observed reappearance of detectable plasma viremia in HIV-infected individuals in whom HAART was discontinued. Moreover, since it is likely that these infected cells die upon activation of virus and that HAART prevents spread of virus to adjacent cells, the observation that this combination of cytokines can markedly induce viral replication in this reservoir may have important implications for the activation-mediated diminution of the latent reservoir of HIV in patients receiving HAART.

scholarly journals Human Immunodeficiency Virus (HIV)–Infected CCR6+ Rectal CD4+ T Cells and HIV Persistence On Antiretroviral Therapy

2019 ◽  
Vol 221 (5) ◽  
pp. 744-755 ◽  
Author(s):  
Jenny L Anderson ◽  
Gabriela Khoury ◽  
Rémi Fromentin ◽  
Ajantha Solomon ◽  
Nicolas Chomont ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
People Living With Hiv ◽  
Hiv Persistence ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Living With Hiv

Abstract Background Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy. Methods Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry. Results Integrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines. Conclusions HIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.

scholarly journals HIV DNA Subspecies Persist in both Activated and Resting Memory CD4+ T Cells during Antiretroviral Therapy

2014 ◽  
Vol 88 (6) ◽  
pp. 3516-3526 ◽  
Author(s):  
J. M. Murray ◽  
J. J. Zaunders ◽  
K. L. McBride ◽  
Y. Xu ◽  
M. Bailey ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Hiv Dna ◽  
Memory Cd4 T Cells

scholarly journals Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy

mBio ◽  
2021 ◽  
Author(s):  
Cristina Gálvez ◽  
Judith Grau-Expósito ◽  
Victor Urrea ◽  
Bonaventura Clotet ◽  
Vicenç Falcó ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Relative Contribution ◽  
Latently Infected ◽  
Cell Subpopulations ◽  
Main Barrier ◽  
Hiv 1

The main barrier for HIV-1 cure is the presence of latently infected CD4 + T cells. Although various cell subpopulations have been identified as major HIV-1 reservoir cells, the relative contribution of infected CD4 subpopulations in the HIV-1 reservoir remains largely unknown.

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