Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus expansion after antigenic stimulation of primary CD4+ T lymphocytes

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1853-1856
Author(s):  
Reinhard Maier ◽  
Marı́a Matilde Bartolomé-Rodrı́guez ◽  
Corinne Moulon ◽  
Hans Ulrich Weltzien ◽  
Andreas Meyerhans
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Lymphocytes ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Antigenic Stimulation ◽  
Productive Infection ◽  
Immunodeficiency Virus ◽  
Kinetics Of ◽  
Stimulation Of

The chemokine receptors CCR5 and CXCR4 are coreceptors for the human immunodeficiency virus (HIV) and determine the cell tropism of different HIV strains. Previous studies on their regulation were performed under conditions of unspecific T-lymphocyte stimulation and provided conflicting results. To mimick physiologic conditions, highly purified primary Staphylococcus enterotoxin B (SEB)-reactive CD4 T lymphocytes were stimulated in the presence of autologous antigen-presenting cells and the kinetics of CCR5 and CXCR4 surface expression and HIV replication were studied. Both chemokine receptors were transiently up-regulated with maximal expression at day 3 after stimulation. The stimulated T cells were equally susceptible to productive infection with R5-and X4-tropic virus strains. Thus, antigenic stimulation of T cells promotes efficient replication of both, T cell-tropic and macrophage-tropic HIV.

Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus expansion after antigenic stimulation of primary CD4+ T lymphocytes

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1853-1856 ◽  
Author(s):  
Reinhard Maier ◽  
Marı́a Matilde Bartolomé-Rodrı́guez ◽  
Corinne Moulon ◽  
Hans Ulrich Weltzien ◽  
Andreas Meyerhans
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Lymphocytes ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Antigenic Stimulation ◽  
Productive Infection ◽  
Immunodeficiency Virus ◽  
Kinetics Of ◽  
Stimulation Of

Abstract The chemokine receptors CCR5 and CXCR4 are coreceptors for the human immunodeficiency virus (HIV) and determine the cell tropism of different HIV strains. Previous studies on their regulation were performed under conditions of unspecific T-lymphocyte stimulation and provided conflicting results. To mimick physiologic conditions, highly purified primary Staphylococcus enterotoxin B (SEB)-reactive CD4 T lymphocytes were stimulated in the presence of autologous antigen-presenting cells and the kinetics of CCR5 and CXCR4 surface expression and HIV replication were studied. Both chemokine receptors were transiently up-regulated with maximal expression at day 3 after stimulation. The stimulated T cells were equally susceptible to productive infection with R5-and X4-tropic virus strains. Thus, antigenic stimulation of T cells promotes efficient replication of both, T cell-tropic and macrophage-tropic HIV.

scholarly journals Increased Density of Human Immunodeficiency Virus Type 1 Coreceptors CCR5 and CXCR4 on the Surfaces of CD4+ T Cells and Monocytes of Patients with Schistosoma mansoni Infection

2003 ◽  
Vol 71 (11) ◽  
pp. 6668-6671 ◽  
Author(s):  
W. Evan Secor ◽  
Amil Shah ◽  
Pauline M. N. Mwinzi ◽  
Bryson A. Ndenga ◽  
Caroline O. Watta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Surface ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Peripheral Blood ◽  
Chemokine Receptors ◽  
Blood Samples ◽  
Immunodeficiency Virus

ABSTRACT Distribution of chemokine receptors CCR5 and CXCR4, which are also coreceptors for human immunodeficiency virus type 1 invasion of cells, was measured on the surfaces of CD4+ T cells and monocytes in peripheral blood samples from a group of Kenyan car washers. Patients with active schistosomiasis displayed higher cell surface densities of these receptors than did cured schistosomiasis patients.

scholarly journals Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 585-594 ◽  
Author(s):  
Linda A. Trimble ◽  
Judy Lieberman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus ◽  
Specific Cytotoxicity

Although human immunodeficiency virus (HIV)-infected subjects without acquired immunodeficiency syndrome have a high frequency of HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently lack detectable HIV-specific cytotoxicity. However, this effector function becomes readily apparent after overnight culture. To investigate reasons for T-cell dysfunction, we analyzed T-cell expression of the cytolytic protease granzyme A and of CD3ζ, the signaling component of the T-cell receptor complex. An increased proportion of CD4 and CD8 T cells from HIV-infected donors contain granzyme A, consistent with the known increased frequency of activated T cells. In 28 HIV-infected donors with mild to advanced immunodeficiency, a substantial fraction of circulating T cells downmodulated CD3ζ (fraction of T cells expressing CD3ζ, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3ζ expression is downregulated more severely in CD8 than CD4 T cells, decreases early in infection, and correlates with declining CD4 counts and disease stage. CD3ζ expression increases over 6 to 16 hours of culture in an interleukin-2–dependent manner, coincident with restoration of viral-specific cytotoxicity. Impaired T-cell receptor signaling may help explain why HIV-specific cytotoxic T lymphocytes fail to control HIV replication.

scholarly journals Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4+ T Cells

2005 ◽  
Vol 79 (4) ◽  
pp. 2199-2210 ◽  
Author(s):  
Yan Zhou ◽  
Haili Zhang ◽  
Janet D. Siliciano ◽  
Robert F. Siliciano
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Reverse Transcription ◽  
Half Life ◽  
Immunodeficiency Virus ◽  
Kinetics Of ◽  
Hiv 1

ABSTRACT In untreated human immunodeficiency virus type 1 (HIV-1) infection, most viral genomes in resting CD4+ T cells are not integrated into host chromosomes. This unintegrated virus provides an inducible latent reservoir because cellular activation permits integration, virus gene expression, and virus production. It remains controversial whether HIV-1 is stable in this preintegration state. Here, we monitored the fate of HIV-1 in resting CD4+ cells by using a green fluorescent protein (GFP) reporter virus carrying an X4 envelope. After virus entry into resting CD4+ T cells, both rescuable virus gene expression, visualized with GFP, and rescuable virion production, assessed by p24 release, decayed with a half-life of 2 days. In these cells, reverse transcription goes to completion over 2 to 3 days, and 50% of the viruses that have entered undergo functional decay before reverse transcription is complete. We distinguished two distinct but closely related factors contributing to loss of rescuable virus. First, some host cells undergo virus-induced apoptosis upon viral entry, thereby reducing the amount of rescuable virus. Second, decay processes directly affecting the virus both before and after the completion of reverse transcription contribute to the loss of rescuable virus. The functional half-life of full-length, integration-competent reverse transcripts is only 1 day. We propose that rapid intracellular decay processes compete with early steps in viral replication in infected CD4+ T cells. Decay processes dominate in resting CD4+ T cells as a result of the slow kinetics of reverse transcription and blocks at subsequent steps. Therefore, the reservoir of unintegrated HIV-1 in recently infected resting CD4+ T cells is highly labile.

scholarly journals Follicular Helper T Cells Are Major Human Immunodeficiency Virus-2 Reservoirs and Support Productive Infection

2019 ◽  
Vol 221 (1) ◽  
pp. 122-126 ◽  
Author(s):  
Ana Godinho-Santos ◽  
Russell B Foxall ◽  
Ana V Antão ◽  
Bárbara Tavares ◽  
Tiago Ferreira ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Ex Vivo ◽  
Immune Deficiency Syndrome ◽  
Productive Infection ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Immunodeficiency Virus

Abstract Follicular helper T cells (Tfh), CD4 lymphocytes critical for efficient antibody responses, have been shown to be key human immunodeficiency virus (HIV)-1 reservoirs. Human immunodeficiency virus-2 infection represents a unique naturally occurring model for investigating Tfh role in HIV/acquired immune deficiency syndrome, given its slow rate of CD4 decline, low to undetectable viremia, and high neutralizing antibody titers throughout the disease course. In this study, we investigated, for the first time, Tfh susceptibility to HIV-2 infection by combining in vitro infection of tonsillar Tfh with the ex vivo study of circulating Tfh from HIV-2-infected patients. We reveal that Tfh support productive HIV-2 infection and are preferential viral targets in HIV-2-infected individuals.

scholarly journals Modalities of Interleukin-7-Induced Human Immunodeficiency Virus Permissiveness in Quiescent T Lymphocytes

2002 ◽  
Vol 76 (18) ◽  
pp. 9103-9111 ◽  
Author(s):  
Odile Ducrey-Rundquist ◽  
Mireille Guyader ◽  
Didier Trono
Keyword(s):  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Lymphocytes ◽  
T Cell Homeostasis ◽  
Activated T Cells ◽  
Hiv Susceptibility ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Cell Cycle Status

ABSTRACT The metabolic and cell cycle status of primary T lymphocytes conditions their susceptibility to human immunodeficiency virus (HIV) and HIV-derived vectors. While in fully quiescent T lymphocytes the reverse transcription and nuclear import of these retroelements are impaired, leading to an abortive infection, various stimuli can induce a state of virus permissiveness. Here, we studied the modalities by which interleukin-7 (IL-7), an important controller of T-cell homeostasis, exerts this effect. IL-7-exposed cord blood T lymphocytes proliferated and were efficiently transduced by HIV-derived vectors. In contrast, similarly treated adult peripheral blood (PB) T lymphocytes failed to divide, and only a subset of these cells became infectible. HIV-resistant and -sensitive subsets of IL-7-treated PB T lymphocytes differed in cell cycle status but not in naïve, memory, or activation phenotypes. Nuclear factor of activated T cells was not induced by IL-7, and cyclosporine did not prevent HIV-mediated gene transfer. Furthermore, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked IL-7-induced cell survival and Bcl-2 synthesis but had no effect on the acquisition of HIV susceptibility, suggesting that IL-7-induced HIV type 1 permissiveness is not mediated by the PI-3 K pathway and that, perhaps, the Jak/STAT5 pathway, the other known mediator of IL-7-triggered signaling in T cells, governs this process.

scholarly journals Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

2016 ◽  
Vol 90 (17) ◽  
pp. 7607-7617 ◽  
Author(s):  
Hélène Dutartre ◽  
Mathieu Clavière ◽  
Chloé Journo ◽  
Renaud Mahieux
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Escape ◽  
Productive Infection ◽  
T Lymphotropic Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4+T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targetedin vivoby both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4+T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading totrans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs (“cis-infection”) and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs.

scholarly journals Physiological Levels of Virion-Associated Human Immunodeficiency Virus Type 1 Envelope Induce Coreceptor-Dependent Calcium Flux

2006 ◽  
Vol 81 (4) ◽  
pp. 1773-1785 ◽  
Author(s):  
Marta Melar ◽  
David E. Ott ◽  
Thomas J. Hope
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Chemokine Receptors ◽  
Calcium Flux ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Hiv Entry ◽  
The One ◽  
Signaling Activation

ABSTRACT Human immunodeficiency virus (HIV) entry into target cells requires the engagement of receptor and coreceptor by envelope glycoprotein (Env). Coreceptors CCR5 and CXCR4 are chemokine receptors that generate signals manifested as calcium fluxes in response to binding of the appropriate ligand. It has previously been shown that engagement of the coreceptors by HIV Env can also generate Ca2+ fluxing. Since the sensitivity and therefore the physiological consequence of signaling activation in target cells is not well understood, we addressed it by using a microscopy-based approach to measure Ca2+ levels in individual CD4+ T cells in response to low Env concentrations. Monomeric Env subunit gp120 and virion-bound Env were able to activate a signaling cascade that is qualitatively different from the one induced by chemokines. Env-mediated Ca2+ fluxing was coreceptor mediated, coreceptor specific, and CD4 dependent. Comparison of the observed virion-mediated Ca2+ fluxing with the exact number of viral particles revealed that the viral threshold necessary for coreceptor activation of signaling in CD4+ T cells was quite low, as few as two virions. These results indicate that the physiological levels of virion binding can activate signaling in CD4+ T cells in vivo and therefore might contribute to HIV-induced pathogenesis.

Interleukin-7–treated naive T cells can be productively infected by T-cell–adapted and primary isolates of human immunodeficiency virus 1

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3310-3318 ◽  
Author(s):  
Carolyn M. Steffens ◽  
Elizabeth Z. Managlia ◽  
Alan Landay ◽  
Lena Al-Harthi
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Productive Infection ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Naïve T Cell ◽  
Naive T Cell

Abstract Although human immunodeficiency virus (HIV)gag/pol DNA can be detected in naive T cells, whether naive T cells can be productively infected by HIV is still questionable. Given that interleukin-7 (IL-7) is a prospective therapeutic immunomodulator for the treatment of HIV, we evaluated the effect of IL-7 on promoting naive T-cell infection of laboratory-adapted (IIIB), M-tropic, and primary isolates of HIV. Initially, we determined that the 3 cell surface markers widely used to identify naive T cells (CD45RA+CD45RO−, CD45RA+CD62L+, and CD45RO−CD27+CD95low) are all equivalent in T-cell receptor excision circle content, a marker for the replicative history of a cell as well as for de novo T cells. We therefore used CD45RA+CD45RO− expression to define naive T cells in this study. We demonstrate that although untreated or IL-2–treated naive T cells are not productively infected by HIV, IL-7 pretreatment mediated the productive infection of laboratory-adapted, M-tropic, and primary isolates of HIV as determined by p24 core antigen production. This up-regulation was between 8- and 58-fold, depending on the HIV isolate used. IL-7 pretreatment of naive T cells also potently up-regulated surface expression of CXCR4 but not CCR5 and mediated the expansion of naive T cells without the acquisition of the primed CD45RO phenotype. Collectively, these data indicate that IL-7 augments naive T-cell susceptibility to HIV and that under the appropriate environmental milieu, naive T cells may be a source of HIV productive infection. This information needs to be considered in evaluating IL-7 as an immunomodulator for HIV-infected patients.

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