-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant
While antiretroviral therapy (ART) can reduce HIV replication, it does not eradicate the virus from an infected individual. Replication-competent viruses persist on ART and our incomplete understanding of these viral reservoirs greatly complicates the generation of a cure for HIV. In this study we performed, for the first time, hematopoietic stem cell transplant (HSCT) in the established model of SIV infection of rhesus macaques (RM). The HSC originating from the bone marrow were collected before SIV infection. After SIV infection, RM were treated with ART for several weeks to reduce viral replication before performing a total body irradiation and a transplant with their own, pre-infection, stem cells. The irradiation eliminated 94–99% of the circulating CD4+ T-cells, the main cell target of HIV/SIV infection. A successful engraftment of the HSC was observed and blood viral reservoirs were drastically reduced. However, when ART was interrupted, a rapid rebound of plasma viremia was observed in two out of three transplanted RM indicating that the massive reset of the hematopoietic compartment was not sufficient to eliminate the total-body virus reservoir in the setting of short term ART. This model of HSCT in SIV-infected RM provides a new platform to investigate HIV eradication strategies.
Vyšlo v časopise: Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004406
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004406Souhrn
While antiretroviral therapy (ART) can reduce HIV replication, it does not eradicate the virus from an infected individual. Replication-competent viruses persist on ART and our incomplete understanding of these viral reservoirs greatly complicates the generation of a cure for HIV. In this study we performed, for the first time, hematopoietic stem cell transplant (HSCT) in the established model of SIV infection of rhesus macaques (RM). The HSC originating from the bone marrow were collected before SIV infection. After SIV infection, RM were treated with ART for several weeks to reduce viral replication before performing a total body irradiation and a transplant with their own, pre-infection, stem cells. The irradiation eliminated 94–99% of the circulating CD4+ T-cells, the main cell target of HIV/SIV infection. A successful engraftment of the HSC was observed and blood viral reservoirs were drastically reduced. However, when ART was interrupted, a rapid rebound of plasma viremia was observed in two out of three transplanted RM indicating that the massive reset of the hematopoietic compartment was not sufficient to eliminate the total-body virus reservoir in the setting of short term ART. This model of HSCT in SIV-infected RM provides a new platform to investigate HIV eradication strategies.
Zdroje
1. ChunTW, StuyverL, MizellSB, EhlerLA, MicanJA, et al. (1997) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94 : 13193–13197.
2. FinziD, HermankovaM, PiersonT, CarruthLM, BuckC, et al. (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278 : 1295–1300.
3. ChunTW, JustementJS, MurrayD, HallahanCW, MaenzaJ, et al. (2010) Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 24 : 2803–2808.
4. DaveyRTJr, BhatN, YoderC, ChunTW, MetcalfJA, et al. (1999) HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A 96 : 15109–15114.
5. HutterG, NowakD, MossnerM, GanepolaS, MussigA, et al. (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360 : 692–698.
6. AllersK, HutterG, HofmannJ, LoddenkemperC, RiegerK, et al. (2011) Evidence for the cure of HIV infection by CCR5Delta32/Delta32 stem cell transplantation. Blood 117 : 2791–2799.
7. YuklSA, BoritzE, BuschM, BentsenC, ChunTW, et al. (2013) Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog 9: e1003347.
8. HenrichTJ, HuZ, LiJZ, SciaranghellaG, BuschMP, et al. (2013) Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J Infect Dis 207 : 1694–1702.
9. Henrich TJ, Hanhauser E, Sirigano M, Davis B, Lee T-H, et al. (IAS 2013) In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation. IAS 2013. Kuala Lumpur, Malaysia.
10. EvansDT, SilvestriG (2013) Nonhuman primate models in AIDS research. Curr Opin HIV AIDS 8 : 255–261.
11. DinosoJB, RabiSA, BlanksonJN, GamaL, MankowskiJL, et al. (2009) A simian immunodeficiency virus-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol 83 : 9247–9257.
12. KearneyM, SpindlerJ, ShaoW, MaldarelliF, PalmerS, et al. (2011) Genetic diversity of simian immunodeficiency virus encoding HIV-1 reverse transcriptase persists in macaques despite antiretroviral therapy. J Virol 85 : 1067–1076.
13. NorthTW, HigginsJ, DeereJD, HayesTL, VillalobosA, et al. (2010) Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. J Virol 84 : 2913–2922.
14. ShytajIL, NorelliS, ChirulloB, Della CorteA, CollinsM, et al. (2012) A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model. PLoS Pathog 8: e1002774.
15. MalphettesM, CarcelainG, Saint-MezardP, LeblondV, AltesHK, et al. (2003) Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age. Blood 101 : 1891–1897.
16. Henrich TJ, Hanhauser E, Sirigano M, Li JZ, Lichterfeld M, et al. (2014) HIV-1 Rebound Following Allogeneic Stem Cell Transplantation and Treatment Interruption. CROI 2014. Boston.
17. LarsenCP, PageA, LinzieKH, RussellM, DeaneT, et al. (2010) An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching. Am J Transplant 10 : 2396–2409.
18. KeanLS, AdamsAB, StrobertE, HendrixR, GangappaS, et al. (2007) Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Am J Transplant 7 : 320–335.
19. HofmanMJ, HigginsJ, MatthewsTB, PedersenNC, TanC, et al. (2004) Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. Antimicrob Agents Chemother 48 : 3483–3490.
20. NorthTW, Van RompayKK, HigginsJ, MatthewsTB, WadfordDA, et al. (2005) Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. J Virol 79 : 7349–7354.
21. SoderbergK, DenekampL, NikiforowS, SautterK, DesrosiersRC, et al. (2002) A nucleotide substitution in the tRNA(Lys) primer binding site dramatically increases replication of recombinant simian immunodeficiency virus containing a human immunodeficiency virus type 1 reverse transcriptase. J Virol 76 : 5803–5806.
22. MillerWP, SrinivasanS, Panoskaltsis-MortariA, SinghK, SenS, et al. (2010) GVHD after haploidentical transplantation: a novel, MHC-defined rhesus macaque model identifies CD28 − CD8+ T cells as a reservoir of breakthrough T-cell proliferation during costimulation blockade and sirolimus-based immunosuppression. Blood 116 : 5403–5418.
23. SilvestriG, SodoraDL, KoupRA, PaiardiniM, O'NeilSP, et al. (2003) Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18 : 441–452.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Out-of-Sequence Signal 3 as a Mechanism for Virus-Induced Immune Suppression of CD8 T Cell ResponsesČlánek RNF26 Temporally Regulates Virus-Triggered Type I Interferon Induction by Two Distinct MechanismsČlánek Mouse, but Not Human, ApoB-100 Lipoprotein Cholesterol Is a Potent Innate Inhibitor of Pneumolysin
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2014 Číslo 9- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
-
Všetky články tohto čísla
- Virus Control Goes Epigenetic
- The Role of Iron in Prion Disease and Other Neurodegenerative Diseases
- The Ins and Outs of Rust Haustoria
- Prion Strains and Amyloid Polymorphism Influence Phenotypic Variation
- Teaching Fido New ModiFICation Tricks
- Can Enhance Infection in Mosquitoes: Implications for Malaria Control?
- MIF Contributes to Associated Immunopathogenicity Development
- Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant
- Bacillus Calmette-Guerin Infection in NADPH Oxidase Deficiency: Defective Mycobacterial Sequestration and Granuloma Formation
- EhCoactosin Stabilizes Actin Filaments in the Protist Parasite
- Molecular Insights Into the Evolutionary Pathway of O1 Atypical El Tor Variants
- LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of
- Structural Correlates of Rotavirus Cell Entry
- Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction
- The Effects of Vaccination and Immunity on Bacterial Infection Dynamics
- Myeloid Derived Hypoxia Inducible Factor 1-alpha Is Required for Protection against Pulmonary Infection
- Functional Characterisation of Germinant Receptors in and Presents Novel Insights into Spore Germination Systems
- Global Analysis of Neutrophil Responses to Reveals a Self-Propagating Inflammatory Program
- Host Cell Invasion by Apicomplexan Parasites: The Junction Conundrum
- Comparative Phenotypic Analysis of the Major Fungal Pathogens and
- Unravelling the Multiple Functions of the Architecturally Intricate β-galactosidase, BgaA
- Sialylation of Prion Protein Controls the Rate of Prion Amplification, the Cross-Species Barrier, the Ratio of PrP Glycoform and Prion Infectivity
- Symbionts Commonly Provide Broad Spectrum Resistance to Viruses in Insects: A Comparative Analysis of Strains
- Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10
- Identification and Characterisation of a Hyper-Variable Apoplastic Effector Gene Family of the Potato Cyst Nematodes
- Crimean-Congo Hemorrhagic Fever Virus Entry into Host Cells Occurs through the Multivesicular Body and Requires ESCRT Regulators
- Age-Dependent Enterocyte Invasion and Microcolony Formation by
- CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression
- Functional Fluorescent Protein Insertions in Herpes Simplex Virus gB Report on gB Conformation before and after Execution of Membrane Fusion
- The Tudor Domain Protein Spindlin1 Is Involved in Intrinsic Antiviral Defense against Incoming Hepatitis B Virus and Herpes Simplex Virus Type 1
- Transgenic Analysis of the MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability
- Evidence for a Transketolase-Mediated Metabolic Checkpoint Governing Biotrophic Growth in Rice Cells by the Blast Fungus
- Incomplete Deletion of IL-4Rα by LysM Reveals Distinct Subsets of M2 Macrophages Controlling Inflammation and Fibrosis in Chronic Schistosomiasis
- Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from , a Southern Hemisphere Sea Louse Affecting Farmed Fish
- Out-of-Sequence Signal 3 as a Mechanism for Virus-Induced Immune Suppression of CD8 T Cell Responses
- Strong Epistatic Selection on the RNA Secondary Structure of HIV
- Hematopoietic but Not Endothelial Cell MyD88 Contributes to Host Defense during Gram-negative Pneumonia Derived Sepsis
- Delineation of Interfaces on Human Alpha-Defensins Critical for Human Adenovirus and Human Papillomavirus Inhibition
- Exploitation of Reporter Strains to Probe the Impact of Vaccination at Sites of Infection
- RNF26 Temporally Regulates Virus-Triggered Type I Interferon Induction by Two Distinct Mechanisms
- Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4 and CD8 T Cell Responses in a Process Dependent on IL-10
- MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to
- Reactive Oxygen Species Regulate Caspase-11 Expression and Activation of the Non-canonical NLRP3 Inflammasome during Enteric Pathogen Infection
- Evolution of Plastic Transmission Strategies in Avian Malaria
- A New Human 3D-Liver Model Unravels the Role of Galectins in Liver Infection by the Parasite
- Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function
- Mouse, but Not Human, ApoB-100 Lipoprotein Cholesterol Is a Potent Innate Inhibitor of Pneumolysin
- The Cofilin Phosphatase Slingshot Homolog 1 (SSH1) Links NOD1 Signaling to Actin Remodeling
- Kaposi's Sarcoma Herpesvirus MicroRNAs Induce Metabolic Transformation of Infected Cells
- Reorganization of the Endosomal System in -Infected Cells: The Ultrastructure of -Induced Tubular Compartments
- Distinct Dictation of Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality via Triggering TLR3 and TLR4 Signal Pathways
- Exploitation of the Complement System by Oncogenic Kaposi's Sarcoma-Associated Herpesvirus for Cell Survival and Persistent Infection
- The Secreted Peptide PIP1 Amplifies Immunity through Receptor-Like Kinase 7
- Structural Insight into Host Recognition by Aggregative Adherence Fimbriae of Enteroaggregative
- The CD14CD16 Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Malaria
- Infection Induces Expression of a Mosquito Salivary Protein (Agaphelin) That Targets Neutrophil Function and Inhibits Thrombosis without Impairing Hemostasis
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- The Secreted Peptide PIP1 Amplifies Immunity through Receptor-Like Kinase 7
- Symbionts Commonly Provide Broad Spectrum Resistance to Viruses in Insects: A Comparative Analysis of Strains
- MIF Contributes to Associated Immunopathogenicity Development
- The Ins and Outs of Rust Haustoria
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy