HIV-DNA Vaccination Following Transfer of a Large Number of Activated T Cells Enhances Immunoresponses Against HIV-1

2000 ◽  
Vol 13 (1) ◽  
pp. 3-8 ◽  
Author(s):  
KENJI HAMAJIMA ◽  
KE-QIN XIN ◽  
JUN FUKUSHIMA ◽  
JUN YANG ◽  
AKIKO HONSHO ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Vaccination ◽  
Activated T Cells ◽  
Hiv Dna ◽  
Hiv 1

scholarly journals Reciprocal regulation of the nuclear factor of activated T cells and HIV-1

2004 ◽  
Vol 5 (3) ◽  
pp. 158-167 ◽  
Author(s):  
F Pessler ◽  
RQ Cron
Keyword(s):  
T Cells ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Reciprocal Regulation ◽  
Hiv 1

scholarly journals HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-30 ◽  
Author(s):  
Charles R. Rinaldo
Keyword(s):  
T Cells ◽  
Virus Replication ◽  
Virus Transmission ◽  
Antigen Presenting Cells ◽  
Activated T Cells ◽  
Infection Processes ◽  
The Many ◽  
Antigen Presenting ◽  
Hiv 1 ◽  
Virus Subtype

Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1transinfection of CD4+T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct,cisinfection of either APC or T cells, ortransinfection between T cells. Such APC-to-T celltransinfection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of thesetransinfection processes and their role in natural HIV-1 infection.

scholarly journals HIV-1 latency in activated T-cells

Retrovirology ◽  
2013 ◽  
Vol 10 (S1) ◽  
Author(s):  
Ben Berkhout
Keyword(s):  
T Cells ◽  
Activated T Cells ◽  
Hiv 1

scholarly journals Next-Generation Sequencing in a Direct Model of HIV Infection Reveals Important Parallels to and Differences from In Vivo Reservoir Dynamics

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Marilia Rita Pinzone ◽  
Maria Paola Bertuccio ◽  
D. Jake VanBelzen ◽  
Ryan Zurakowski ◽  
Una O’Doherty
Keyword(s):  
T Cells ◽  
Next Generation Sequencing ◽  
Cd4 T Cells ◽  
Next Generation ◽  
Activated T Cells ◽  
Selection Pressures ◽  
Hiv Dna ◽  
Generation Sequencing

ABSTRACT Next-generation sequencing (NGS) represents a powerful tool to unravel the genetic make-up of the HIV reservoir, but limited data exist on its use in vitro. Moreover, most NGS studies do not separate integrated from unintegrated DNA, even though selection pressures on these two forms should be distinct. We reasoned we could use NGS to compare the infection of resting and activated CD4 T cells in vitro to address how the metabolic state affects reservoir formation and dynamics. To address these questions, we obtained HIV sequences 2, 4, and 8 days after NL4-3 infection of metabolically activated and quiescent CD4 T cells (cultured with 2 ng/ml interleukin-7). We compared the composition of integrated and total HIV DNA by isolating integrated HIV DNA using pulsed-field electrophoresis before performing sequencing. After a single-round infection, the majority of integrated HIV DNA was intact in both resting and activated T cells. The decay of integrated intact proviruses was rapid and similar in both quiescent and activated T cells. Defective forms accumulated relative to intact ones analogously to what is observed in vivo. Massively deleted viral sequences formed more frequently in resting cells, likely due to lower deoxynucleoside triphosphate (dNTP) levels and the presence of multiple restriction factors. To our surprise, the majority of these deleted sequences did not integrate into the human genome. The use of NGS to study reservoir dynamics in vitro provides a model that recapitulates important aspects of reservoir dynamics. Moreover, separating integrated from unintegrated HIV DNA is important in some clinical settings to properly study selection pressures. IMPORTANCE The major implication of our work is that the decay of intact proviruses in vitro is extremely rapid, perhaps as a result of enhanced expression. Gaining a better understanding of why intact proviruses decay faster in vitro might help the field identify strategies to purge the reservoir in vivo. When used wisely, in vitro models are a powerful tool to study the selective pressures shaping the viral landscape. Our finding that massively deleted sequences rarely succeed in integrating has several ramifications. It demonstrates that the total HIV DNA can differ substantially in character from the integrated HIV DNA under certain circumstances. The presence of unintegrated HIV DNA has the potential to obscure selection pressures and confound the interpretation of clinical studies, especially in the case of trials involving treatment interruptions.

No Increase in Activated T Cells and Limited Increase in Adenovirus-specific T Cells in Colon and Rectal Mucosa Following HIV-1 DNA/rAd5 Immunization

2014 ◽  
Vol 30 (S1) ◽  
pp. A48-A48
Author(s):  
Stephen De Rosa ◽  
Nicole Frahm ◽  
Gabriela Diaz ◽  
Paul Newling ◽  
Daryl Morris ◽  
...  
Keyword(s):  
T Cells ◽  
Rectal Mucosa ◽  
Activated T Cells ◽  
Hiv 1

Regulation of nuclear factor of activated T cells by phosphotyrosyl-specific phosphatase activity: a positive effect on HIV-1 long terminal repeat–driven transcription and a possible implication of SHP-1

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2390-2400 ◽  
Author(s):  
Jean-François Fortin ◽  
Benoit Barbeau ◽  
Gilles A. Robichaud ◽  
Marie-Ève Paré ◽  
Anne-Marie Lemieux ◽  
...  
Keyword(s):  
T Cells ◽  
Long Terminal Repeat ◽  
Nuclear Translocation ◽  
Interleukin 2 ◽  
Dominant Negative ◽  
Terminal Repeat ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Nfat Activation ◽  
Hiv 1

Abstract Although protein tyrosine phosphatase (PTP) inhibitors used in combination with other stimuli can induce interleukin 2 (IL-2) production in T cells, a direct implication of nuclear factor of activated T cells (NFAT) has not yet been demonstrated. This study reports that exposure of leukemic T cells and human peripheral blood mononuclear cells to bis-peroxovanadium (bpV) PTP inhibitors markedly induce activation and nuclear translocation of NFAT. NFAT activation by bpV was inhibited by the immunosuppressive drugs FK506 and cyclosporin A, as well as by a specific peptide inhibitor of NFAT activation. Mobility shift assays showed specific induction of the NFAT1 member by bpV molecules. The bpV-mediated NFAT activation was observed to be important for the up-regulation of the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) and the IL-2 promoter; NFAT1 was demonstrated to be particularly important in bpV-dependent positive action on HIV-1 LTR transcription. The active participation of p56lck, ZAP-70, p21ras, and calcium in the bpV-mediated signaling cascade leading to NFAT activation was confirmed, using deficient cell lines and dominant-negative mutants. Finally, overexpression of wild-type SHP-1 resulted in a greatly diminished activation of NFAT by bpV, suggesting an involvement of SHP-1 in the regulation of NFAT activation. These data were confirmed by constitutive NFAT translocation observed in Jurkat cells stably expressing a dominant-negative version of SHP-1. The study proposes that PTP activity attenuates constitutive kinase activities that otherwise would lead to constant NFAT activation and that this activation is participating in HIV-1 LTR stimulation by PTP inhibition.

scholarly journals Prolonged Post-Treatment Virologic Control and Complete Seroreversion after Advanced HIV-1 Infection

2020 ◽  
Author(s):  
Analia Uruena ◽  
Isabel Cassetti ◽  
Neena Kashyap ◽  
Claire Deleage ◽  
Jacob D Estes ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Mononuclear Cells ◽  
Brain Biopsy ◽  
Post Treatment ◽  
Hiv Diagnosis ◽  
Hiv Reservoir ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Hiv 1

Abstract Background Possible human immunodeficiency virus (HIV)-1 clearance has been rarely reported. Here we describe a unique case of an HIV-positive, combination antiretroviral therapy (cART)-experienced woman with prior acquired immunodeficiency syndrome (AIDS) who has not experienced viral rebound for over 12 years since discontinuing cART. Methods Leukapheresis, colonoscopy, and lymph node excision were performed for detailed examination of virologic (including HIV reservoir) and immunologic features. Comparisons were made with chronically infected patients and healthy controls. Results No HIV-specific antibodies were detected in serum. Plasma HIV RNA levels were <0.2 copies/mL and, except for low-frequency HIV DNA + cells in lymph node tissue (1 copy/3 x 10 6 cells), HIV antigen could not be detected by quantitative virus outgrowth (<0.0025 infectious units/10 6 CD4 + T cells) or by most measurements of HIV RNA or DNA in blood, lymph node or gut-associated mononuclear cells. HIV-specific T-cell responses were detectable, but low. Brain imaging revealed a prior biopsy site and persistent white matter disease since 1996. HIV DNA + cells in the 1996 brain biopsy specimen confirmed her identity and initial HIV diagnosis. Conclusions This represents the first report of complete seroreversion, prolonged post-treatment virus suppression, a profoundly small HIV reservoir and persistent HIV-specific T cells in an adult with prior AIDS.

scholarly journals Majority of CD4+ T cells from peripheral blood of HIV-1-infected individuals contain only one HIV DNA molecule

2011 ◽  
Vol 108 (27) ◽  
pp. 11199-11204 ◽  
Author(s):  
L. Josefsson ◽  
M. S. King ◽  
B. Makitalo ◽  
J. Brannstrom ◽  
W. Shao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Dna Molecule ◽  
Hiv Dna ◽  
Hiv 1

Hematopoietic stem cell–engrafted NOD/SCID/IL2Rγnull mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 212-218 ◽  
Author(s):  
Satoru Watanabe ◽  
Kazuo Terashima ◽  
Shinrai Ohta ◽  
Shigeo Horibata ◽  
Misako Yajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Animal Model ◽  
T Cells ◽  
Immune Responses ◽  
Lymphoid Tissues ◽  
Hematopoietic Stem ◽  
Specific Antibodies ◽  
Hiv Dna ◽  
Hiv 1 ◽  
Hiv Aids

AbstractCritical to the development of an effective HIV/AIDS model is the production of an animal model that reproduces long-lasting active replication of HIV-1 followed by elicitation of virus-specific immune responses. In this study, we constructed humanized nonobese diabetic/severe combined immunodeficiency (NOD/SCID)/interleukin-2 receptor γ-chain knockout (IL2Rγnull) (hNOG) mice by transplanting human cord blood–derived hematopoietic stem cells that eventually developed into human B cells, T cells, and other monocytes/macrophages and 4 dendritic cells associated with the generation of lymphoid follicle–like structures in lymphoid tissues. Expressions of CXCR4 and CCR5 antigens were recognized on CD4+ cells in peripheral blood, the spleen, and bone marrow, while CCR5 was not detected on thymic CD4+ T cells. The hNOG mice showed marked, long-lasting viremia after infection with both CCR5- and CXCR4-tropic HIV-1 isolates for more than the 40 days examined, with R5 virus–infected animals showing high levels of HIV-DNA copies in the spleen and bone marrow, and X4 virus–infected animals showing high levels of HIV-DNA copies in the thymus and spleen. Furthermore, we detected both anti–HIV-1 Env gp120– and Gag p24–specific antibodies in animals showing a high rate of viral infection. Thus, the hNOG mice mirror human systemic HIV infection by developing specific antibodies, suggesting that they may have potential as an HIV/AIDS animal model for the study of HIV pathogenesis and immune responses.

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