scholarly journals Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells

2017 ◽  
Vol 13 (2) ◽  
pp. e1006163 ◽  
Author(s):  
Jason A. Neidleman ◽  
Joseph C. Chen ◽  
Nargis Kohgadai ◽  
Janis A. Müller ◽  
Anders Laustsen ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Stromal Fibroblasts

Circulating integrin α 4 β 7 + CD4 T cells are enriched for proliferative transcriptional programs in HIV infection

FEBS Letters ◽  
2021 ◽  
Author(s):  
Yashavanth S. Lakshmanappa ◽  
Jamin W. Roh ◽  
Niharika N. Rane ◽  
Ashok R. Dinasarapu ◽  
Daphne D. Tran ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd4 T Cells

scholarly journals Identification of novel genes involved in apoptosis of HIV-infected macrophages using unbiased genome-wide screening

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simon X. M. Dong ◽  
Frederick S. Vizeacoumar ◽  
Kalpana K. Bhanumathy ◽  
Nezeka Alli ◽  
Cristina Gonzalez-Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Respiratory Chain ◽  
Cd4 T Cells ◽  
Chain Complex ◽  
Respiratory Chain Complex ◽  
Complex Ii ◽  
Genome Wide ◽  
Latently Infected ◽  
Induced Apoptosis

Abstract Background Macrophages, besides resting latently infected CD4+ T cells, constitute the predominant stable, major non-T cell HIV reservoirs. Therefore, it is essential to eliminate both latently infected CD4+ T cells and tissue macrophages to completely eradicate HIV in patients. Until now, most of the research focus is directed towards eliminating latently infected CD4+ T cells. However, few approaches have been directed at killing of HIV-infected macrophages either in vitro or in vivo. HIV infection dysregulates the expression of many host genes essential for the survival of infected cells. We postulated that exploiting this alteration may yield novel targets for the selective killing of infected macrophages. Methods We applied a pooled shRNA-based genome-wide approach by employing a lentivirus-based library of shRNAs to screen novel gene targets whose inhibition should selectively induce apoptosis in HIV-infected macrophages. Primary human MDMs were infected with HIV-eGFP and HIV-HSA viruses. Infected MDMs were transfected with siRNAs specific for the promising genes followed by analysis of apoptosis by flow cytometry using labelled Annexin-V in HIV-infected, HIV-exposed but uninfected bystander MDMs and uninfected MDMs. The results were analyzed using student’s t-test from at least four independent experiments. Results We validated 28 top hits in two independent HIV infection models. This culminated in the identification of four target genes, Cox7a2, Znf484, Cstf2t, and Cdk2, whose loss-of-function induced apoptosis preferentially in HIV-infected macrophages. Silencing these single genes killed significantly higher number of HIV-HSA-infected MDMs compared to the HIV-HSA-exposed, uninfected bystander macrophages, indicating the specificity in the killing of HIV-infected macrophages. The mechanism governing Cox7a2-mediated apoptosis of HIV-infected macrophages revealed that targeting respiratory chain complex II and IV genes also selectively induced apoptosis of HIV-infected macrophages possibly through enhanced ROS production. Conclusions We have identified above-mentioned novel genes and specifically the respiratory chain complex II and IV genes whose silencing may cause selective elimination of HIV-infected macrophages and eventually the HIV-macrophage reservoirs. The results highlight the potential of the identified genes as targets for eliminating HIV-infected macrophages in physiological environment as part of an HIV cure strategy.

scholarly journals Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4 + T cells

2014 ◽  
Vol 92 (9) ◽  
pp. 770-780 ◽  
Author(s):  
Peilin Li ◽  
Katsuya Fujimoto ◽  
Lilly Bourguingnon ◽  
Steven Yukl ◽  
Steven Deeks ◽  
...  
Keyword(s):  
T Cells ◽  
Hyaluronic Acid ◽  
Hiv Infection ◽  
Cd4 T Cells

Quasilinearization-Lagrangian method to solve the HIV infection model of CD4 $$^+$$ + T cells

SeMA Journal ◽  
2017 ◽  
Vol 75 (2) ◽  
pp. 271-283 ◽  
Author(s):  
Kourosh Parand ◽  
Zahra Kalantari ◽  
Mehdi Delkhosh
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Lagrangian Method ◽  
Infection Model ◽  
Hiv Infection Model

scholarly journals HLA-E Up-Regulation Induced by HIV Infection May Directly Contribute to CD94-Mediated Impairment of NK Cells

2005 ◽  
Vol 18 (2) ◽  
pp. 269-276 ◽  
Author(s):  
F. Martini ◽  
C. Agrati ◽  
G. D'Offizi ◽  
F. Poccia
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Nk Cells ◽  
Cd4 T Cells ◽  
Nk Cell ◽  
Treatment Interruption ◽  
Cell Number ◽  
Hiv Replication

Alterations in NK cell numbers and function have been repeatedly shown during HIV infection. In this study, NK cell number and MHC class I expression on CD4+ T cells were studied in HIV patients at different stages of disease progression. An increased expression of HLA-E was seen on CD4+ T cells. In parallel, a reduced number of CD94+ NK cells was observed in advanced disease stages. Moreover, a decline in CD94 expression on NK cells was observed at the HIV replication peak in patients undergoing antiretroviral treatment interruption, suggesting a role of viral replication on NK cells alterations. In vitro HIV infection induced a rapid down-regulation of HLA-A,B,C expression, paralleled by an increased expression of HLA-E surface molecules, the formal ligands of CD94 NK receptors. HIV-infected HLA-E expressing cells were able to inhibit NK cell cytotoxicity through HLA-E expression, since cytotoxicity was restored by antibody masking experiments. These data indicate that the CD94/HLA-E interaction may contribute to NK cell dysfunction in HIV infection, suggesting a role of HIV replication in this process.

scholarly journals Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model

2020 ◽  
Vol 69 (1) ◽  
pp. 28-40 ◽  
Author(s):  
Ross Cromarty ◽  
Alexander Sigal ◽  
Lenine Julie Liebenberg ◽  
Lyle Robert Mckinnon ◽  
Salim Safurdeen Abdool Karim ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
Drug Targets ◽  
Complex Nature ◽  
Peripheral Blood Mononuclear ◽  
Established Risk Factor ◽  
Anti Inflammatory

Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV infection, have an immune quiescent phenotype defined by reduced immune activation and inflammatory cytokines at the genital tract. Therefore, the aim of this study was to create an immune quiescent environment using immunomodulatory drugs to mitigate HIV infection. Using an in vitro peripheral blood mononuclear cell (PBMC) model, we found that inflammation was induced using phytohemagglutinin and Toll-like receptor (TLR) agonists Pam3CSK4 (TLR1/2), lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8). After treatment with anti-inflammatory drugs, ibuprofen (IBF) and betamethasone (BMS), PBMCs were exposed to HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines to assess inflammation. Flow cytometry was used to measure immune activation (CD38, HLA-DR and CCR5) and HIV infection (p24 production) of CD4+ T cells. BMS potently suppressed inflammation (soluble cytokines, p<0.05) and immune activation (CD4+ T cells, p<0.05). BMS significantly reduced HIV infection of CD4+ T cells only in the LPS (0.98%) and unstimulated (1.7%) conditions (p<0.02). In contrast, IBF had minimal anti-inflammatory and immunosuppressive but no anti-HIV effects. BMS demonstrated potent anti-inflammatory effects, regardless of stimulation condition. Despite uniform immunosuppression, BMS differentially affected HIV infection according to the stimulation conditions, highlighting the complex nature of these interactions. Together, these data underscore the importance of interrogating inflammatory signaling pathways to identify novel drug targets to mitigate HIV infection.

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