scholarly journals Possible hidden cause of human immunodeficiency virus type 1 latency and role of interferon

Mediscope ◽  
2016 ◽  
Vol 3 (2) ◽  
pp. 11-17
Author(s):  
Nursarat Ahmed ◽  
Kazuki Miura
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Latent human immunodeficiency virus type 1 (HIV-1) infected cells under antiretroviral therapy are reported to be resting memory CD4+ T cells; however, the mechanisms of HIV-1 latency is unclear. We demonstrate that long-term culture of interleukin-2-dependent CD4+ T cells with a memory phenotype mimicked latently HIV-1-infected cells in the presence of interferon-?. These cells are mostly resting and contained HIV-1 proviruses that could be re-activated by stimulation. Our findings suggest a potential role of type-1 interferon in HIV-1 latency.Mediscope Vol. 3, No. 2: July 2016, Pages 11-17

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 Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7645-7657 ◽  
Author(s):  
Keyang Chen ◽  
Jialing Huang ◽  
Chune Zhang ◽  
Sophia Huang ◽  
Giuseppe Nunnari ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Innate Immunity ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-α/β signal transduction pathway, IFN-α can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-α will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-α-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-α/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.

scholarly journals Naive CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-competent Human Immunodeficiency Virus Type 1

2019 ◽  
Vol 69 (11) ◽  
pp. 1919-1925 ◽  
Author(s):  
Jennifer M Zerbato ◽  
Deborah K McMahon ◽  
Michelle D Sobolewski ◽  
John W Mellors ◽  
Nicolas Sluis-Cremer
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Virus Production ◽  
Major Barrier ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Background The latent human immunodeficiency virus type 1 (HIV-1) reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naive (TN) vs resting memory CD4+ T cells, it is widely hypothesized that this reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-1–infected individuals on suppressive therapy. Methods CD4+ TN and TCM cells were purified from the blood of 7 HIV-1–infected individuals. We quantified total HIV-1 DNA in the CD4+ TN and TCM cells. Extracellular virion-associated HIV-1 RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 monoclonal antibodies (mAbs), phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat, or romidepsin. Results HIV-1 DNA was significantly higher in TCM compared to TN cells (2179 vs 684 copies/106 cells, respectively). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV-1 RNA levels were similar between TCM and TN cells (15 135 vs 18 290 copies/mL, respectively). In 4/7 donors, virus production was higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. Conclusions Although the frequency of HIV-1 infection is lower in TN compared to TCM cells, as much virus is produced from the TN population after latency reversal. This finding suggests that quantifying HIV-1 DNA alone may not predict the size of the inducible latent reservoir and that TN cells may be an important reservoir of latent HIV-1.

scholarly journals Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection

2020 ◽  
Vol 71 (11) ◽  
pp. e735-e743 ◽  
Author(s):  
Andrey Tokarev ◽  
Lyle R McKinnon ◽  
Amélie Pagliuzza ◽  
Aida Sivro ◽  
Tosin E Omole ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Acute Infection ◽  
Immunodeficiency Virus ◽  
Memory Cd4 T Cells ◽  
Hiv 1

Abstract Background Establishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex α4β7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection. Methods Integrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I–III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin β7 (β7negative and β7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for β7-defined subsets at acute infection and in uninfected controls. Results In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both β7high and β7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7high cells were enriched in integrated and total HIV-1 DNA compared to β7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7negative and β7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7high cells was correlated with their activation. Conclusions β7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.

scholarly journals Intercellular Adhesion Molecule 1 (ICAM-1), but Not ICAM-2 and -3, Is Important for Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission

2009 ◽  
Vol 83 (9) ◽  
pp. 4195-4204 ◽  
Author(s):  
Jian-Hua Wang ◽  
Constance Kwas ◽  
Li Wu
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Intercellular Adhesion ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Dendritic cells (DCs) play a critical role in cell-to-cell-mediated transmission of human immunodeficiency virus type 1 (HIV-1). Interactions between intercellular adhesion molecules (ICAMs) and their ligands facilitate DC-T-cell contact. The interaction between ICAM-1 on DCs and leukocyte function-associated molecule 1 (LFA-1) on CD4+ T cells has been proposed to be important for DC-mediated HIV-1 transmission. Given that DCs and T cells express multiple ICAMs and binding ligands, the relative importance of ICAMs in DC-mediated HIV-1 transmission remains to be defined. Here, we examine the role of ICAM-1, -2, and -3 in DC-mediated HIV-1 transmission to various types of target cells including primary CD4+ T cells. The expression levels of ICAMs and their ligands on immature and mature DCs and various types of HIV-1 target cells were measured by flow cytometry. Blocking ICAM-1 in DCs with specific monoclonal antibodies and small interfering RNA impaired DC-mediated HIV-1 transmission. DC-mediated viral transmission was significantly inhibited when both ICAM-1 on DCs and LFA-1 on CD4+ T cells were blocked. However, blockade of ICAM-1 on target cells did not significantly inhibit DC-mediated HIV-1 transmission. Ectopic expression and antibody blocking suggest that DC-mediated HIV-1 transmission to primary CD4+ T cells is independent of ICAM-2 and ICAM-3. Taken together, our data clarified the role of ICAMs in DC-mediated HIV-1 transmission to CD4+ T cells.

scholarly journals Virus-Specific Interleukin-17-Producing CD4+ T Cells Are Detectable in Early Human Immunodeficiency Virus Type 1 Infection

2008 ◽  
Vol 82 (13) ◽  
pp. 6767-6771 ◽  
Author(s):  
Feng Yun Yue ◽  
Asad Merchant ◽  
Colin M. Kovacs ◽  
Mona Loutfy ◽  
Desmond Persad ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Interleukin 17 ◽  
Immunodeficiency Virus ◽  
Early Human ◽  
Hiv 1

ABSTRACT TH-17 cells have been shown to play a role in bacterial defense, acute inflammation, and autoimmunity. We examined the role of interleukin 17 (IL-17) production in human immunodeficiency virus type 1 (HIV-1) infection. Both HIV-1- and cytomegalovirus (CMV)-specific IL-17-producing CD4+ T cells were detectable in early HIV-1 infection but were reduced to nondetectable levels in chronic and nonprogressive HIV-1 infection. IL-17-producing CMV-specific cells were not detected in blood from HIV-1-uninfected normal volunteers. Virus-specific TH-17 cells could coexpress other cytokines and could express CCR4 or CXCR3. Although the etiology of these cells has yet to be established, we propose that microbial translocation may induce them.

scholarly journals Human Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo

2007 ◽  
Vol 81 (13) ◽  
pp. 6947-6956 ◽  
Author(s):  
Zilin Nie ◽  
Gary D. Bren ◽  
Stacey R. Vlahakis ◽  
Alicia Algeciras Schimnich ◽  
Jason M. Brenchley ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Specific Product ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4+ T cells, predominantly in the CD27+ memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells.

scholarly journals Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

2009 ◽  
Vol 90 (8) ◽  
pp. 1795-1805 ◽  
Author(s):  
Bizhan Romani ◽  
Susan Engelbrecht
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Critical Role ◽  
Cellular Proteins ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the vpr gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

scholarly journals In Vivo Evolution of Human Immunodeficiency Virus Type 1 toward Increased Pathogenicity through CXCR4-Mediated Killing of Uninfected CD4 T Cells

2003 ◽  
Vol 77 (10) ◽  
pp. 5846-5854 ◽  
Author(s):  
Andreas Jekle ◽  
Oliver T. Keppler ◽  
Erik De Clercq ◽  
Dominique Schols ◽  
Mark Weinstein ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The destruction of the immune system by progressive loss of CD4 T cells is the hallmark of AIDS. CCR5-dependent (R5) human immunodeficiency virus type 1 (HIV-1) isolates predominate in the early, asymptomatic stages of HIV-1 infection, while CXCR4-dependent (X4) isolates typically emerge at later stages, frequently coinciding with a rapid decline in CD4 T cells. Lymphocyte killing in vivo primarily occurs through apoptosis, but the importance of apoptosis of HIV-1-infected cells relative to apoptosis of uninfected bystander cells is controversial. Here we show that in human lymphoid tissues ex vivo, apoptosis of uninfected bystander CD4 T cells is a major mechanism of lymphocyte depletion caused by X4 HIV-1 strains but is only a minor mechanism of depletion by R5 strains. Further, X4 HIV-1-induced bystander apoptosis requires the interaction of the viral envelope glycoprotein gp120 with the CXCR4 coreceptor on CD4 T cells. These results emphasize the contribution of bystander apoptosis to HIV-1 cytotoxicity and suggest that in association with a coreceptor switch in HIV disease, T-cell killing evolves from an infection-restricted stage to generalized toxicity that involves a high degree of bystander apoptosis.

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