scholarly journals The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses

2009 ◽  
Author(s):  
Nathalie Arhel ◽  
Martin Lehmann ◽  
Karen Clauß ◽  
G. Ulrich Nienhaus ◽  
Vincent Piguet ◽  
...  
Keyword(s):  
T Cells ◽  
Immunological Synapse ◽  
Human T Cells ◽  
Primate Lentiviruses ◽  
Hiv 1

Disruption of HIV-1 Co-Receptors CCR5 and CXCR4 in Primary Human T Cells and Hematopoietic Stem and Progenitor Cells Using Base Editing

2021 ◽  
Author(s):  
Friederike Knipping ◽  
Gregory A. Newby ◽  
Cindy R. Eide ◽  
Amber N. McElroy ◽  
Sarah C. Nielsen ◽  
...  
Keyword(s):  
T Cells ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Base Editing ◽  
Human T Cells ◽  
Stem And Progenitor Cells ◽  
Hiv 1

Synthesis, Characterization and anti-HIV and Antitumor Activities of New Coumarin Derivatives

2008 ◽  
Vol 63 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Yaseen A. Al-Soud ◽  
Haitham H. Al-Sa’doni ◽  
Houssain A. S. Amajaour ◽  
Kifah S. M. Salih ◽  
Mohammad S. Mubarakb ◽  
...  
Keyword(s):  
T Cells ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Coumarin Derivatives ◽  
Antitumor Activities ◽  
Reverse Transcriptase Inhibitors ◽  
Human T Cells ◽  
Anti Hiv ◽  
Hiv 1

A new series of coumarin and benzofuran derivatives were synthesized as potential non-nucleoside reverse transcriptase inhibitors (NNRTIs) by reacting, separately, 4-bromomethylcoumarins, their sulphonyl chlorides, and ethyl 3-(bromomethyl)-6-methoxy-1-benzofuran-2-carboxylate with different imidazoles and their benzo analogs. The antiviral (HIV-1, HIV-2) properties of the newly synthesized compounds were investigated in vitro and all compounds were found to be inactive, except 10 which showed inhibition of HIV-2 with EC50 > 0.51 μgmL−1. The in vitro cytotoxicity of 17 and 19 was assayed against a panel of tumor cell lines consisting of CD4 human T-cells.

Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes

1993 ◽  
Vol 13 (10) ◽  
pp. 6180-6189 ◽  
Author(s):  
M H Malim ◽  
B R Cullen
Keyword(s):  
T Cells ◽  
Regulation Of Gene Expression ◽  
Nucleocytoplasmic Transport ◽  
Viral Mrnas ◽  
Nuclear Retention ◽  
Human T Cells ◽  
Cellular Factors ◽  
Immunodeficiency Virus ◽  
Nuclear Degradation ◽  
Hiv 1

Although a great deal is known about the regulation of gene expression in terms of transcription, relatively little is known about the modulation of pre-mRNA processing. In this study, we exploited a genetically regulated system, human immunodeficiency virus type 1 (HIV-1) and its trans-activator Rev, to examine events that occur between the synthesis of pre-mRNA in the nucleus and the translation of mRNA in the cytoplasm. Unlike the majority of eukaryotic pre-mRNAs whose introns are efficiently recognized and spliced prior to nucleocytoplasmic transport, HIV-1 mRNAs containing functional introns must be exported to the cytoplasm for the expression of many viral proteins. Using human T cells containing stably integrated proviruses, we demonstrate that such incompletely spliced viral mRNAs are exported to the cytoplasm only in the presence of the Rev trans-activator. In the absence of Rev, these intron-containing RNAs are sequestered in the T-cell nucleus and either spliced or, more commonly, degraded. Because Rev does not inhibit the expression of fully spliced viral mRNA species in T cells, we propose that Rev, rather than inhibiting viral pre-mRNA splicing, is acting here both to prevent the nuclear degradation of HIV-1 pre-mRNAs and to induce their translocation to the cytoplasm. Taken together, these findings indicate that the cellular factors responsible for the nuclear retention of unspliced pre-mRNAs, although most probably splicing factors, do not invariably commit these RNAs to productive splicing and can, instead, program such transcripts for degradation.

Intracellular Expression of Cellular eIF-5A Mutants Inhibits HIV-1 Replication in Human T Cells: A Feasibility Study

1996 ◽  
Vol 7 (15) ◽  
pp. 1861-1869 ◽  
Author(s):  
Uwe Junker ◽  
Dorian Bevec ◽  
Carmen Barske ◽  
Creton Kalfoglou ◽  
Sonia Escaich ◽  
...  
Keyword(s):  
T Cells ◽  
Feasibility Study ◽  
Human T Cells ◽  
Intracellular Expression ◽  
Hiv 1

scholarly journals Role of Cell Surface Glycosaminoglycans of Human T Cells in Human Immunodeficiency Virus Type-1 (HIV-1) Infection

1996 ◽  
Vol 40 (11) ◽  
pp. 827-835 ◽  
Author(s):  
Yukako Ohshiro ◽  
Tsutomu Murakami ◽  
Kazuhiro Matsuda ◽  
Kiyoshi Nishioka ◽  
Keiichi Yoshida ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Surface ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human T Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Cytokine Signals Are Sufficient for HIV-1 Infection of Resting Human T Lymphocytes

1999 ◽  
Vol 189 (11) ◽  
pp. 1735-1746 ◽  
Author(s):  
Derya Unutmaz ◽  
Vineet N. KewalRamani ◽  
Shana Marmon ◽  
Dan R. Littman
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Structure Function ◽  
Human Lymphocytes ◽  
Stable Gene ◽  
Mutant Form ◽  
Primary Cells ◽  
Human T Cells ◽  
Transformed Cell Lines ◽  
Hiv 1

Lentiviral vectors have been advocated to be effective vehicles for the delivery and stable expression of genes in nondividing primary cells. However, certain cell types, such as resting T lymphocytes, are resistant to infection with HIV-1. Establishing parameters for stable gene delivery into primary human lymphocytes and approaches to overcome the resistance of resting T cells to HIV infection may permit potential gene therapy applications, genetic studies of primary cells in vitro, and a better understanding of the stages of the lentiviral life cycle. Here we demonstrate that an HIV-1–derived vector can be used for stable delivery of genes into activated human T cells as well as natural killer and dendritic cells. Remarkably, a sizeable fraction of resting T cells was stably transduced with the HIV-1 vector when cultured with the cytokine interleukin (IL)-2, IL-4, IL-7, or IL-15, or, at a lower level, with IL-6, in the absence of any other stimuli. Resting T cells stimulated with these cytokines could also be infected with replication-competent HIV-1. To test the utility of this system for performing structure–function analysis in primary T cells, we introduced wild-type as well as a mutant form of murine CD28 into human T cells and showed a requirement for the CD28 cytoplasmic domain in costimulatory signaling. The ability to stably express genes of interest in primary T cells will be a valuable tool for genetic and structure–function studies that previously have been limited to transformed cell lines. In addition, the finding that cytokine signals are sufficient to permit transduction of resting T cells with HIV may be relevant for understanding mechanism of HIV-1 transmission and pathogenesis.

scholarly journals FoxP3 Enhances HIV-1 Gene Expression by Modulating NFκB Occupancy at the Long Terminal Repeat in Human T Cells

2007 ◽  
Vol 282 (22) ◽  
pp. 15973-15980 ◽  
Author(s):  
Derek Holmes ◽  
Geoffry Knudsen ◽  
Stephanie Mackey-Cushman ◽  
Lishan Su
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Long Terminal Repeat ◽  
Terminal Repeat ◽  
Human T Cells ◽  
Hiv 1

scholarly journals Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.

1994 ◽  
Vol 179 (2) ◽  
pp. 513-522 ◽  
Author(s):  
T R Kollmann ◽  
M Pettoello-Mantovani ◽  
X Zhuang ◽  
A Kim ◽  
M Hachamovitch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Human T Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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