scholarly journals Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9151
Author(s):  
Mohammad Sadraeian ◽  
Calise Bahou ◽  
Edgar Ferreira da Cruz ◽  
Luíz Mário Ramos Janini ◽  
Ricardo Sobhie Diaz ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Disulfide Bridge ◽  
Therapeutic Strategies ◽  
Oxygen Species ◽  
New Strategy ◽  
Hiv Antigen ◽  
Antibody Conjugates ◽  
Infected Cells ◽  
Hiv 1 ◽  
Antibody Ratio

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

scholarly journals Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates Against HIV Env-Expressing Cells

2020 ◽  
Author(s):  
Mohammad Sadraeian ◽  
Calise Bahou ◽  
Edgar Ferreira da Cruz ◽  
Luíz Mário Ramos Janini ◽  
Ricardo Sobhie Diaz ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Disulfide Bridge ◽  
Therapeutic Strategies ◽  
Oxygen Species ◽  
New Strategy ◽  
Hiv Antigen ◽  
Antibody Conjugates ◽  
Infected Cells ◽  
Hiv 1 ◽  
Antibody Ratio

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

scholarly journals Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488 ◽  
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Retinoic Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Proteins ◽  
Mrna Synthesis ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Abstract HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.

scholarly journals Extracellular Vesicles from Infected Cells Are Released Prior to Virion Release

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 781
Author(s):  
Yuriy Kim ◽  
Gifty A. Mensah ◽  
Sarah Al Sharif ◽  
Daniel O. Pinto ◽  
Heather Branscome ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Viral Proteins ◽  
Extracellular Vesicle ◽  
Virion Release ◽  
Human T Cell ◽  
Rich Media ◽  
T Cell Leukemia Virus ◽  
Infected Cells ◽  
Related Proteins ◽  
Hiv 1

Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia virus-1 (HTLV-1)-infected (HUT102) cells were synchronized in G0. Viral latency was reversed by increasing gene expression with the addition of serum-rich media and inducers. Supernatants and cell pellets were collected post-induction at different timepoints and assayed for extracellular vesicle (EV) and autophagy markers; and for viral proteins and RNAs. Tetraspanins and autophagy-related proteins were found to be differentially secreted in HIV-1- and HTLV-1-infected cells when compared with uninfected controls. HIV-1 proteins were present at 6 h and their production increased up to 24 h. HTLV-1 proteins peaked at 6 h and plateaued. HIV-1 and HTLV-1 RNA production correlated with viral protein expression. Nanoparticle tracking analysis (NTA) showed increase of EV concentration over time in both uninfected and infected samples. Finally, the HIV-1 supernatant from the 6-h samples was found not to be infectious; however, the virus from the 24-h samples was successfully rescued and infectious. Overall, our data indicate that EV release may occur prior to viral release from infected cells, thereby implicating a potentially significant effect of EVs on uninfected recipient cells prior to subsequent viral infection and spread.

scholarly journals HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death

2019 ◽  
Author(s):  
Coralie F Daussy ◽  
Mathilde Galais ◽  
Baptiste Pradel ◽  
Véronique Robert-Hebmann ◽  
Sophie Sagnier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Viral Envelope ◽  
Cd4 T Cell ◽  
Oxygen Species ◽  
Fluorescence Studies ◽  
Selective Autophagy ◽  
Infected Cells ◽  
Hiv 1

AbstractThe immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocytes death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers autophagy, process necessary to subsequent apoptosis, and to production of Reactive Oxygen Species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, catalase and PEX14, upon Env exposure, since the down-regulation of either BECLIN 1 or p62/SQSTM1 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency.

scholarly journals Lipid and nucleocapsid N-protein accumulation in COVID-19 patient lung and infected cells

2021 ◽  
Author(s):  
Anita Grootemaat ◽  
Sanne van der Niet ◽  
Edwin R. Scholl ◽  
Eva Roos ◽  
Bernadette Schurink ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Detection ◽  
Viral Proteins ◽  
Vero Cells ◽  
Therapeutic Strategies ◽  
Protein Accumulation ◽  
N Protein ◽  
Virus Particles ◽  
Cellular Marker ◽  
Infected Cells

The trafficking of coronaviruses in lung of COVID-19 patients is not well understood and virus particles are difficult to find. Here we have visualized virus particles in SARS-CoV-2 infected cells by focusing on viral protein detection, in combination with ultrastructure. We studied how the virus is altering the cell morphology and determined that in Vero cells, lipid filled compartments contained various viral proteins. In these cells, also membrane enclosed multi-virus bodies were visible that contain a different set of viral proteins. We demonstrated that lipid filled compartments are novel viral induced compartments, as no known cellular marker such as lipid droplet or lysosomal marker was present. Using this knowledge, we then studied lung tissue from patients with a fatal SARS-Cov-2 infection, processed in a similar manner. Again we detected lipid filled compartments with viral proteins nsp4 and the stable nucleocapsid N-protein. The presence of these lipid filled compartments with viral proteins induced by SARS-CoV-2 infections, could be why the immune response of the COVID-19 patients is so strong, resulting in a fatal infection, and should be considered for new therapeutic strategies.

scholarly journals The Use of Nanotrap Particles Technology in Capturing HIV-1 Virions and Viral Proteins from Infected Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96778 ◽  
Author(s):  
Elizabeth Jaworski ◽  
Mohammed Saifuddin ◽  
Gavin Sampey ◽  
Nazly Shafagati ◽  
Rachel Van Duyne ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Retinoic Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Proteins ◽  
Mrna Synthesis ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.

scholarly journals Heat Shock Protein–Based Therapeutic Strategies Against Human Immunodeficiency Virus Type Infection

1999 ◽  
Vol 7 (1-2) ◽  
pp. 80-90 ◽  
Author(s):  
B. G. Brenner ◽  
M. A. Wainberg
Keyword(s):  
Human Immunodeficiency Virus ◽  
Heat Shock ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nk Cell ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Life Cycles ◽  
Immunodeficiency Virus ◽  
Hiv 1

Heat shock proteins (hsps) and cyclophilins (CypA) are intracellular chaperone molecules that facilitate protein folding and assembly. These proteins are selectively expressed in cells following exposure to a range of stress stimuli, including viral infection. Hsp species are highly immunogenic, eliciting humoral, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell responses against viruses, tumours, and infectious diseases. This review discusses the roles of stress proteins in immunity and viral life cycles, vis-à-vis the development of Hsp-based therapeutic strategies against human immunodeficiency virus type-1 (HIV-1) infection. Cumulative findings are cited implicating the requirement of CypA in HIV-1 replication and formation of infectious virions. Studies by our group show the upregulated expression of hsp27 and hsp70 during single-cycle HIV infections. These species redistribute to the cell surface following HIV-infection and heat stress, serving as targets for NK and antibody-dependent cellular cytotoxicity. Co-immunoprecipitation and Western blot studies show that hsp27, hsp70, and hsp78 complex with HIV-1 viral proteins intracellularly. Hsp70, hsp56, and CypA are assembled into HIV-1 virions. The ability of hsps to interact with HIV-1 viral proteins, combined with their inherent adjuvant and immunogenic properties, indicates that hsps may serve as vehicles for antigen delivery and the design of vaccines against acquired immunodeficiency syndrome. Infect. Dis. Obstet. Gynecol. 7:80–90, 1999.

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