scholarly journals Single-cell Sequencing Resolves Landscape of Immune cell and Regulatory Mechanisms in HIV-infected immune non-responders

2021 ◽  
Author(s):  
Haiyu Li ◽  
Yujing Wang ◽  
Yue Li ◽  
Yi Yang ◽  
Yuxin Xia ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mitochondrial Function ◽  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Single Cell Sequencing ◽  
Mait Cells ◽  
Highly Active ◽  
Hiv 1

Abstract Immune non-responder (INR) after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infection and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here we performed scRNA-seq and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from Immune nonresponder (INR) and responder (IR) HIV-1-infected subjects. We then describe the mitochondrial function of MAIT by flow cytometry in INRs and IRs. We founded there were diminished frequencies and numbers of MAIT cells in INRs, and MAIT cells from INRs displayed transcriptional profiles associated with the impairment of mitochondrial function and apoptosis signaling. ScATAC-seq and flow cytometry revealed diminished mitochondrial fitness in MAIT cells from INRs, and MAIT had low expression of transcription factor A for mitochondria (TFAM) and PPARA. These findings demonstrate the restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT, which against bacterial co-infections in INRs subjects.

scholarly journals Response to Superantigen Stimulation in Peripheral Blood Mononuclear Cells from Children Perinatally Infected with Human Immunodeficiency Virus and Receiving Highly Active Antiretroviral Therapy

2004 ◽  
Vol 11 (5) ◽  
pp. 957-962 ◽  
Author(s):  
Thomas W. McCloskey ◽  
Viraga Haridas ◽  
Lucy Pontrelli ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACT Our understanding of the pathogenesis of perinatal human immunodeficiency virus (HIV) infection is still evolving. We sought to characterize the response to the bacterial superantigen Staphylococcus enterotoxin B (SEB) of lymphocytes from HIV-infected children receiving treatment with highly active antiretroviral therapy (HAART). Using the flow cytometric methodology, we quantified apoptosis, proliferation, cytokine production, and activation antigen upregulation in CD4 and CD8 T lymphocytes following in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with SEB. The levels of proliferation, CD4 interleukin-2 (IL-2) production, CD8 gamma interferon (IFN-γ) production, and upregulation of CD69 expression by cells from HIV-infected children were indistinguishable from those by cells from controls. However, stimulation with SEB dramatically decreased the ratio of resting apoptotic cells to cycling apoptotic cells in the controls but not in the patients. In addition, unstimulated spontaneous apoptosis of CD4 T cells remained greater in the patients than in the controls. The percentages of IL-2-positive CD8 T cells and IFN-γ-positive CD4 T cells following SEB stimulation were significantly lower in the patients than in the controls. Our multiparameter approach was able to demonstrate differences in lymphocyte superantigen responsiveness in HIV-infected children receiving HAART in comparison to that in uninfected controls, notably, an apoptotic versus a proliferative response to stimulation.

scholarly journals Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention

2012 ◽  
Vol 56 (8) ◽  
pp. 4381-4390 ◽  
Author(s):  
Martha Stefanidou ◽  
Carolina Herrera ◽  
Naomi Armanasco ◽  
Robin J. Shattock
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Productive Infection ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Cellular Models ◽  
Hiv 1

ABSTRACTThe maturation of newly formed human immunodeficiency virus type 1 (HIV-1) virions is a critical step for the establishment of productive infection. We investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV inhibited replication of clade B and clade C isolates in a dose-dependent manner in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV demonstrated inhibitory potency againsttransinfection of T cells byin vitro-derived dendritic cells and by primary dendritic cells that emigrate from penile and cervical tissue explants. No cellular or tissue toxicity was detected in the presence of SQV, suggesting that this drug could be considered for development as a component of an effective microbicide, capable of blocking viral maturation and transmission of HIV-1 at mucosal surfaces.

Cellular Pharmacology of D-d4FC, a Nucleoside Analogue Active against Drug-Resistant HIV

2003 ◽  
Vol 14 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Susan Erickson-Viitanen ◽  
Jing-Tao Wu ◽  
Guoen Shi ◽  
Steven Unger ◽  
Robert W King ◽  
...  
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Hiv Infections ◽  
Peripheral Blood Mononuclear ◽  
Cellular Pharmacology ◽  
Synergistic Interactions ◽  
Highly Active ◽  
Virus Genotypes ◽  
Cytidine Analogue

The backbone of effective highly active antiretroviral therapy regimens for the treatment of HIV infections currently contains at least two nucleosides. Among the features that influence the potency of each component of a regimen and the overall efficacy of the combination are the cellular uptake and bioconversion of nucleoside analogues to their active triphosphate form, and the extent of possible interactions in these steps that might occur when more than one nucleoside is used in a regimen. D-d4FC (Reverset™), a new cytidine analogue with the ability to inhibit many nucleoside-resistant viral variants, was examined for these parameters. In phytohemaglutinin-stimulated human peripheral blood mononuclear cells, D-d4FC was taken up in a rapid (8 h to 50% maximal value), saturable (plateau above 10 μM parent nucleoside concentration) process, resulting in levels of D-d4FC triphosphate that should provide potent antiviral activity against a variety of virus genotypes. Based on measurement of antiviral effects in cell culture, additive and in some cases, synergistic interactions were observed with protease inhibitors, non-nucleoside reverse transcriptase inhibitors or other nucleosides, including cytidine analogues.

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