scholarly journals Short Communication: Preferential Killing of HIV Latently Infected CD4+T Cells by MALT1 Inhibitor

2016 ◽  
Vol 32 (2) ◽  
pp. 174-177 ◽  
Author(s):  
Hongmei Li ◽  
Hui He ◽  
Leyi Gong ◽  
Mingui Fu ◽  
Tony T. Wang
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Short Communication ◽  
Latently Infected

scholarly journals Identification of novel genes involved in apoptosis of HIV-infected macrophages using unbiased genome-wide screening

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simon X. M. Dong ◽  
Frederick S. Vizeacoumar ◽  
Kalpana K. Bhanumathy ◽  
Nezeka Alli ◽  
Cristina Gonzalez-Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Respiratory Chain ◽  
Cd4 T Cells ◽  
Chain Complex ◽  
Respiratory Chain Complex ◽  
Complex Ii ◽  
Genome Wide ◽  
Latently Infected ◽  
Induced Apoptosis

Abstract Background Macrophages, besides resting latently infected CD4+ T cells, constitute the predominant stable, major non-T cell HIV reservoirs. Therefore, it is essential to eliminate both latently infected CD4+ T cells and tissue macrophages to completely eradicate HIV in patients. Until now, most of the research focus is directed towards eliminating latently infected CD4+ T cells. However, few approaches have been directed at killing of HIV-infected macrophages either in vitro or in vivo. HIV infection dysregulates the expression of many host genes essential for the survival of infected cells. We postulated that exploiting this alteration may yield novel targets for the selective killing of infected macrophages. Methods We applied a pooled shRNA-based genome-wide approach by employing a lentivirus-based library of shRNAs to screen novel gene targets whose inhibition should selectively induce apoptosis in HIV-infected macrophages. Primary human MDMs were infected with HIV-eGFP and HIV-HSA viruses. Infected MDMs were transfected with siRNAs specific for the promising genes followed by analysis of apoptosis by flow cytometry using labelled Annexin-V in HIV-infected, HIV-exposed but uninfected bystander MDMs and uninfected MDMs. The results were analyzed using student’s t-test from at least four independent experiments. Results We validated 28 top hits in two independent HIV infection models. This culminated in the identification of four target genes, Cox7a2, Znf484, Cstf2t, and Cdk2, whose loss-of-function induced apoptosis preferentially in HIV-infected macrophages. Silencing these single genes killed significantly higher number of HIV-HSA-infected MDMs compared to the HIV-HSA-exposed, uninfected bystander macrophages, indicating the specificity in the killing of HIV-infected macrophages. The mechanism governing Cox7a2-mediated apoptosis of HIV-infected macrophages revealed that targeting respiratory chain complex II and IV genes also selectively induced apoptosis of HIV-infected macrophages possibly through enhanced ROS production. Conclusions We have identified above-mentioned novel genes and specifically the respiratory chain complex II and IV genes whose silencing may cause selective elimination of HIV-infected macrophages and eventually the HIV-macrophage reservoirs. The results highlight the potential of the identified genes as targets for eliminating HIV-infected macrophages in physiological environment as part of an HIV cure strategy.

scholarly journals Similar frequency and inducibility of intact HIV-1 proviruses in blood and lymph nodes

2020 ◽  
Author(s):  
Alyssa R Martin ◽  
Alexandra M Bender ◽  
Jada Hackman ◽  
Kyungyoon J Kwon ◽  
Briana A Lynch ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Viral Rna ◽  
Latent Reservoir ◽  
Similar Frequency ◽  
Latently Infected ◽  
Infected Cells ◽  
Secondary Lymphoid Organs ◽  
Hiv 1

Abstract Background The HIV-1 latent reservoir (LR) in resting CD4 + T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes. Methods We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from ten HIV-1-infected patients on ART using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. Results The frequencies of CD4 + T cells with intact proviruses were not significantly different in PB vs LN (61vs104/10 6CD4 + cells), and were substantially lower than frequencies of CD4 + T cells with defective proviruses. The frequencies of CD4 + T cells induced to produce high levels of viral RNA were not significantly different in PB vs LN (4.3/10 6 vs 7.9/10 6), but were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples. Conclusions These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs

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 An Anti‐CD45RO Immunotoxin Kills Latently Infected Human Immunodeficiency Virus (HIV) CD4 T Cells in the Blood of HIV‐Positive Persons

2002 ◽  
Vol 185 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Jesús Saavedra‐Lozano ◽  
Cynthia McCoig ◽  
Jinbo Xu ◽  
Yanying Cao ◽  
Philip Keiser ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cd4 T Cells ◽  
Hiv Positive ◽  
Immunodeficiency Virus ◽  
Latently Infected

scholarly journals Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals

2003 ◽  
Vol 100 (4) ◽  
pp. 1908-1913 ◽  
Author(s):  
T.-W. Chun ◽  
J. S. Justement ◽  
R. A. Lempicki ◽  
J. Yang ◽  
G. Dennis ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd4 T Cells ◽  
Latently Infected

Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells

AIDS ◽  
1997 ◽  
Vol 11 (9) ◽  
pp. 1103-1110 ◽  
Author(s):  
Hans-Jürgen Stellbrink ◽  
Jan van Lunzen ◽  
Frank T. Hufert ◽  
Günter Fröschle ◽  
Guido Wolf-Vorbeck ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Hiv Infection ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Rapid Turnover ◽  
Hiv Rna ◽  
Latently Infected ◽  
Infected Lymph Node ◽  
Asymptomatic Hiv
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