Retinoic Acid Improves the Recovery of Replication-Competent Virus from Latent SIV Infected Cells
AuthorOlwenyi, Omalla A
Routhu, Nanda Kishore
Jones, Jace W
Kane, Maureen A
Byrareddy, Siddappa N
MetadataShow full item record
AbstractThe accurate estimation and eradication of Human Immunodeficiency Virus (HIV) viral reservoirs is limited by the incomplete reactivation of cells harboring the latent replication-competent virus. We investigated whether the in vitro and in vivo addition of retinoic acid (RA) enhances virus replication and improves the detection of latent virus. Peripheral blood mononuclear cells (PBMCs) from naive and anti-retroviral therapy (ART)-treated SIV-infected rhesus macaques (RMs) were cultured in vitro with anti-CD3/CD28 + IL-2 in the presence/absence of RA. Viral RNA and p27 levels were quantified using RT-qPCR and ELISA, respectively. Viral reservoirs were estimated using the Tat/Rev-Induced Limited Dilution Assay (TILDA) and Quantitative Viral Outgrowth Assay (QVOA). In vitro and in vivo measures revealed that there was also an increase in viral replication in RA-treated versus without RA conditions. In parallel, the addition of RA to either CD3/CD28 or phorbol myristate acetate (PMA)/ionomycin during QVOA and TILDA, respectively, was shown to augment reactivation of the replication-competent viral reservoir in anti-retroviral therapy (ART)-suppressed RMs as shown by a greater than 2.3-fold increase for QVOA and 1 to 2-fold increments for multi-spliced RNA per million CD4+ T cells. The use of RA can be a useful approach to enhance the efficiency of current protocols used for in vitro and potentially in vivo estimates of CD4+ T cell latent reservoirs. In addition, flow cytometry analysis revealed that RA improved estimates of various viral reservoir assays by eliciting broad CD4 T-cell activation as demonstrated by elevated CD25 and CD38 but reduced CD69 and PD-1 expressing cells.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/13772
- Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.
- Authors: Avalos CR, Abreu CM, Queen SE, Li M, Price S, Shirk EN, Engle EL, Forsyth E, Bullock BT, Mac Gabhann F, Wietgrefe SW, Haase AT, Zink MC, Mankowski JL, Clements JE, Gama L
- Issue date: 2017 Aug 15
- Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques.
- Authors: Abreu CM, Veenhuis RT, Avalos CR, Graham S, Parrilla DR, Ferreira EA, Queen SE, Shirk EN, Bullock BT, Li M, Metcalf Pate KA, Beck SE, Mangus LM, Mankowski JL, Mac Gabhann F, O'Connor SL, Gama L, Clements JE
- Issue date: 2019 Aug 20
- Infectious Virus Persists in CD4<sup>+</sup> T Cells and Macrophages in Antiretroviral Therapy-Suppressed Simian Immunodeficiency Virus-Infected Macaques.
- Authors: Abreu CM, Veenhuis RT, Avalos CR, Graham S, Queen SE, Shirk EN, Bullock BT, Li M, Metcalf Pate KA, Beck SE, Mangus LM, Mankowski JL, Clements JE, Gama L
- Issue date: 2019 Aug 1
- Antibody-Mediated CD4 Depletion Induces Homeostatic CD4<sup>+</sup> T Cell Proliferation without Detectable Virus Reactivation in Antiretroviral Therapy-Treated Simian Immunodeficiency Virus-Infected Macaques.
- Authors: Kumar NA, McBrien JB, Carnathan DG, Mavigner M, Mattingly C, White ER, Viviano F, Bosinger SE, Chahroudi A, Silvestri G, Paiardini M, Vanderford TH
- Issue date: 2018 Nov 15
- Short-Term Pegylated Interferon α2a Treatment Does Not Significantly Reduce the Viral Reservoir of Simian Immunodeficiency Virus-Infected, Antiretroviral Therapy-Treated Rhesus Macaques.
- Authors: Palesch D, Bosinger SE, Mavigner M, Billingsley JM, Mattingly C, Carnathan DG, Paiardini M, Chahroudi A, Vanderford TH, Silvestri G
- Issue date: 2018 Jul 15