Animal models in HIV cure research

Abstract Current HIV antiretroviral therapy (ART) successfully inhibits viral replication in the majority of HIV-infected individuals. However, ART is not curative and lifelong adherence is required. Despite the undisputed benefit of ART, long-lived latently infected cells that carry HIV-integrated DNA remain. Hence, upon ART interruption, HIV-infected subjects experience viral rebound. Interestingly, similar disease course occurs in the well-characterised animal model of SIV-infected non-human primates. Using these animal models to investigate the mechanisms involved in the generation of latently infected cells, define the phenotypic and anatomical nature of persistent viral reservoirs, and test novel interventions for viral eradication, is critical for strengthening our understanding of HIV persistence and developing novel therapeutics aimed at curing HIV. In this review, we discuss the current animal models used in AIDS cure research, with a particular focus on non-human primates, and outline the experimental strategies explored in the quest for virus eradication.

• Publication year

  2015

• Venue

  Journal of virus eradication

• Publication date

  2015-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S2055-6640(20)31149-3PMID 27482392PMCID 4946666
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat.

  2014cited by this paper
• Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys

  2014cited by this paper
• Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation

  2014cited by this paper
• Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant

  2014cited by this paper
• Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques

  2014cited by this paper
• In Vivo Blockade of the PD-1 Receptor Suppresses HIV-1 Viral Loads and Improves CD4+ T Cell Levels in Humanized Mice

  2013cited by this paper
• Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of AIDS virus suppression, residual virus, and curative strategies

  2013cited by this paper
• Immune clearance of highly pathogenic SIV infection

  2013cited by this paper
• Immune activation and HIV persistence: implications for curative approaches to HIV infection

  2013cited by this paper
• PD-1 Blockade in Chronically HIV-1-Infected Humanized Mice Suppresses Viral Loads

  2013cited by this paper
• Systemic effects of inflammation on health during chronic HIV infection.

  2013cited by this paper
• Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques.

  2013cited by this paper
• Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation.

  2013cited by this paper
• Absence of detectable HIV-1 viremia after treatment cessation in an infant.

  2013cited by this paper
• Molecular signatures of T-cell inhibition in HIV-1 infection

  2013cited by this paper
• Nonhuman primate models in AIDS research

  2013cited by this paper
• Immune targeting of PD-1(hi) expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques.

  2013cited by this paper
• In Vivo Blockade of the Programmed Cell Death-1 Pathway Using Soluble Recombinant PD-1-Fc Enhances CD4+ and CD8+ T Cell Responses but Has Limited Clinical Benefit

  2013cited by this paper
• Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

  2012cited by this paper
• The evolving epidemiology of HIV/AIDS

  2012cited by this paper
• A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model

  2012cited by this paper
• Humanized mice for immune system investigation: progress, promise and challenges

  2012cited by this paper
• Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation.

  2012cited by this paper
• HIV: Shock and kill

  2012cited by this paper
• Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy.

  2011cited by this paper
• HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS.

  2011cited by this paper
• Generation of HIV Latency in Humanized BLT Mice

  2011cited by this paper
• Immunodeficiency lentiviral infections in natural and non-natural hosts.

  2011cited by this paper
• Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation.

  2011cited by this paper
• Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy.

  2010cited by this paper
• Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines.

  2010cited by this paper
• Evidence for the cure of HIV infection by CCR 5 { Delta } 32 / { Delta } 32 stem cell transplantation

  2010cited by this paper
• Systemic Administration of Antiretrovirals Prior to Exposure Prevents Rectal and Intravenous HIV-1 Transmission in Humanized BLT Mice

  2010cited by this paper
• Synergistic Activation of HIV-1 Expression by Deacetylase Inhibitors and Prostratin: Implications for Treatment of Latent Infection

  2009cited by this paper
• Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors

  2009cited by this paper
• HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

  2009influential reference
• Higher risk of AIDS or death in patients with lower CD4 cell counts after virally suppressive HAART

  2009cited by this paper
• Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection

  2009cited by this paper
• Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation.

  2009cited by this paper
• Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

  2008cited by this paper
• Enhancing SIV-Specific Immunity In Vivo by PD-1 Blockade

  2008cited by this paper
• Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy.

  2008cited by this paper
• Life and death in the cART era.

  2008cited by this paper
• Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1

  2007cited by this paper
• Microbial translocation is a cause of systemic immune activation in chronic HIV infection

  2006cited by this paper
• Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation.

  2006cited by this paper
• Microbial translocation is a cause of systemic immune activation in chronic HIV infection

  2006cited by this paper
• Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

  2004cited by this paper
• Polyamides reveal a role for repression in latency within resting T cells of HIV-infected donors.

  2004cited by this paper
• CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract

  2004cited by this paper
• Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells

  2003cited by this paper
• Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: Intrinsic stability predicts lifelong persistence

  2003cited by this paper
• Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-κB and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies

  2002cited by this paper
• Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy

  2000cited by this paper
• Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy

  1999cited by this paper
• Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS.

  1984cited by this paper
• Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.

  1984cited by this paper
• Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).

  1983cited by this paper
• Detection , Isolation , and Continuous Production of Cytopathic Retroviruses ( HTLV-III ) from Patients with AIDS and Pre-AIDS

  year unknowncited by this paper

• Animal models in human surgery and implant innovation: ethical considerations and scientific advancements

  2025cites this paper
• Lessons for Understanding Central Nervous System HIV Reservoirs from the Last Gift Program

  2022cites this paper
• The CD8+ T Cell Noncytotoxic Antiviral Responses

  2021cites this paper
• Impacts of HIV Cure Interventions on Viral Reservoirs in Tissues

  2019cites this paper
• Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

  2018cites this paper
• Mechanisms of CD8+ T cell‐mediated suppression of HIV/SIV replication

  2018cites this paper
• Whole body MRI of the non-human primate using a clinical 3T scanner: initial experiences.

  2017cites this paper