Martin Delaney Collaboratory to Eradicate HIV-1 Infection

Summary

Principal Investigator: David M Margolis
Abstract: DESCRIPTION (provided by applicant): Despite the clinical success of antiretroviral therapy (ART), more people contract human immunodeficiency virus (HIV) infection daily than initiate ART. The difficulties of lifelong ART - particularly in the developing world - make the eradication of HIV imperative. But clearance of a retroviral infection for patients on ART is a herculean task. While much is known about HIV persistence despite ART, many puzzles remain. New tools to address latent infection must replace the paradigms and models used to develop ART. Existing cellular and animal models that represent HIV latency in vivo require further development, and while latent provirus can be purged in the laboratory, a testable, comprehensive therapeutic strategy is not at hand. Therefore we propose the Martin Delaney Collaboratory to Eradicate HIV-1 Infection, a close collaboration of 21 exceptional investigators who have collectively led the field of HIV latency over the last 10 years. To maximize success, we will work across four areas of research to develop the infrastructure and systems needed to define eradication therapies, identify new molecules with therapeutic potential and provide a proof-of-concept for a small molecule based eradication strategy in animal models. Objective 1 will identify the molecular mechanisms underlying viral persistence and latency;Objective 2 will identify drug candidates and therapeutic strategies to reduce the latent viral pool;Objective 3 will establish informative animal model systems to evaluate latency and test therapeutic strategies;and finally. Objective 4 will perform studies in humans to delineate the basis for viral persistence. Three cores will assist research projects with pharmacology, molecular assays, and sequence and expression analysis. An administrative core will assure coordination, and maintain the focus of this experienced and potent group towards translational product development. As a group, we are committed to pooling our resources and expertise to transcend the normal constraints of academic research. Of note, the expertise and durable commitment of Merck Research Laboratories will be critical to delivering therapeutic advances. We are convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection.
Funding Period: 2011-07-08 - 2016-06-30
more information: NIH RePORT

Top Publications

  1. pmc Screening for noise in gene expression identifies drug synergies
    Roy D Dar
    The Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA
    Science 344:1392-6. 2014
  2. pmc Emerging strategies to deplete the HIV reservoir
    Nancie M Archin
    Institute for Global Health and Infectious Diseases, and Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, USA
    Curr Opin Infect Dis 27:29-35. 2014
  3. pmc Real-world impact of neurocognitive deficits in acute and early HIV infection
    Katie L Doyle
    Joint Doctoral Program in Clinical Psychology, San Diego State University and University of California, San Diego, CA, USA
    J Neurovirol 19:565-73. 2013
  4. pmc Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States
    Gabriel A Wagner
    University of California San Diego, La Jolla, California
    J Infect Dis 209:1032-8. 2014
  5. pmc Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure
    Ya Chi Ho
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 155:540-51. 2013
  6. ncbi An integrated overview of HIV-1 latency
    Debbie S Ruelas
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 155:519-29. 2013
  7. pmc Antibody response to Achromobacter xylosoxidans during HIV infection is associated with lower CD4 levels and increased lymphocyte activation
    Erick T Tatro
    Department of Psychiatry, University of California San Diego, La Jolla, California, USA
    Clin Vaccine Immunol 21:46-50. 2014
  8. pmc HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model
    Jenna B Honeycutt
    Division of Infectious Diseases, Center for AIDS Research, University of North Carolina School of Medicine, 120 Mason Farm Rd, CB 7042, Genetic Medicine Building 2044, Chapel Hill, NC, USA
    Retrovirology 10:121. 2013
  9. pmc Reactivation of latent HIV-1 in central memory CD4⁺ T cells through TLR-1/2 stimulation
    Camille L Novis
    Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Emma Eccles Jones Medical Research Building, Salt Lake City, UT 84112, USA
    Retrovirology 10:119. 2013
  10. pmc Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation
    Alexandra Duverger
    Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
    J Virol 88:364-76. 2014

Detail Information

Publications66

  1. pmc Screening for noise in gene expression identifies drug synergies
    Roy D Dar
    The Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA
    Science 344:1392-6. 2014
    ..Noise-modulating chemicals may provide novel probes for the physiological consequences of noise and an unexplored axis for drug discovery, allowing enhanced control over diverse cell-fate decisions. ..
  2. pmc Emerging strategies to deplete the HIV reservoir
    Nancie M Archin
    Institute for Global Health and Infectious Diseases, and Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, USA
    Curr Opin Infect Dis 27:29-35. 2014
    ..This review highlights recent studies undertaken to further advance the search for successful approaches to eradicate HIV infection...
  3. pmc Real-world impact of neurocognitive deficits in acute and early HIV infection
    Katie L Doyle
    Joint Doctoral Program in Clinical Psychology, San Diego State University and University of California, San Diego, CA, USA
    J Neurovirol 19:565-73. 2013
    ....
  4. pmc Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States
    Gabriel A Wagner
    University of California San Diego, La Jolla, California
    J Infect Dis 209:1032-8. 2014
    ..We used ultradeep sequencing (UDS) to estimate the frequency of DI in a primary infection cohort of predominantly men who have sex with men (MSM)...
  5. pmc Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure
    Ya Chi Ho
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 155:540-51. 2013
    ..The identification of replication-competent noninduced proviruses indicates that the size of the latent reservoir-and, hence, the barrier to cure-may be up to 60-fold greater than previously estimated...
  6. ncbi An integrated overview of HIV-1 latency
    Debbie S Ruelas
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 155:519-29. 2013
    ..In this Review, we discuss HIV-1 latency and the mechanisms that allow this pathogenic retrovirus to hide and persist by exploiting the cellular vehicles of immunological memory. ..
  7. pmc Antibody response to Achromobacter xylosoxidans during HIV infection is associated with lower CD4 levels and increased lymphocyte activation
    Erick T Tatro
    Department of Psychiatry, University of California San Diego, La Jolla, California, USA
    Clin Vaccine Immunol 21:46-50. 2014
    ..01). HIV-positive individuals had higher anti-A. xylosoxidans IgG titers than HIV-uninfected individuals (P = 0.04). The results suggest an abnormal adaptive immune activation to gut microflora during HIV infection. ..
  8. pmc HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model
    Jenna B Honeycutt
    Division of Infectious Diseases, Center for AIDS Research, University of North Carolina School of Medicine, 120 Mason Farm Rd, CB 7042, Genetic Medicine Building 2044, Chapel Hill, NC, USA
    Retrovirology 10:121. 2013
    ..Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages...
  9. pmc Reactivation of latent HIV-1 in central memory CD4⁺ T cells through TLR-1/2 stimulation
    Camille L Novis
    Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Emma Eccles Jones Medical Research Building, Salt Lake City, UT 84112, USA
    Retrovirology 10:119. 2013
    ..Memory CD4⁺ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4⁺ T cells has not been studied...
  10. pmc Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation
    Alexandra Duverger
    Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
    J Virol 88:364-76. 2014
    ....
  11. pmc Absence of detectable HIV-1 viremia after treatment cessation in an infant
    Deborah Persaud
    From the Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore D P, C Z, Y H C, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick M P, and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda T W C all in Maryland the Department of Pediatrics, University of Mississippi Medical Center, Jackson H G the University of California San Diego, La Jolla, and the Veterans Affairs San Diego Healthcare System, San Diego M S, D R and the Department of Pediatrics, Program in Molecular Medicine, and Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester K L
    N Engl J Med 369:1828-35. 2013
    ..This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection. ..
  12. pmc The effect of cell subset isolation method on gene expression in leukocytes
    Nadejda Beliakova-Bethell
    Department of Medicine, University of California San Diego, La Jolla, California, 92093
    Cytometry A 85:94-104. 2014
    ..Thus, FACS is the recommended method for isolation of leukocyte subsets for gene expression studies since this method results in the purest subset populations and does not appear to induce a stress response...
  13. pmc Tristetraprolin expression and microRNA-mediated regulation during simian immunodeficiency virus infection of the central nervous system
    Jonathan Liu
    Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, 733 N, Broadway, Miller Research Building Rm, 829, Baltimore, MD 21205, USA
    Mol Brain 6:40. 2013
    ..This control is lost during progression to disease. In this study, we assessed TTP regulation and association with cytokine regulation in the brain during SIV infection...
  14. pmc SIV replication is directly downregulated by four antiviral miRNAs
    Jeanne M Sisk
    Department of Molecular and Comparative Pathobiology, Edward D, Miller Research Building, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
    Retrovirology 10:95. 2013
    ..We examined whether specific host miRNAs directly target SIV RNA early in infection and might be induced via type I interferon pathways...
  15. pmc HIV latency and integration site placement in five cell-based models
    Scott Sherrill-Mix
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Retrovirology 10:90. 2013
    ....
  16. pmc Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitors
    Mary E Manson McManamy
    Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
    Antivir Chem Chemother 23:145-9. 2014
    ..Here, we review the different HDAC inhibitors that have been studied in HIV-1 latency and their therapeutic potential in reactivating latent HIV-1. ..
  17. pmc A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy
    Adam M Spivak
    University of Utah, Salt Lake City
    Clin Infect Dis 58:883-90. 2014
    ..In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4(+) T cells at concentrations achieved in vivo...
  18. pmc IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV
    Kathryn M Monroe
    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA
    Science 343:428-32. 2014
    ..These findings provide insights into a key host pathway that plays a central role in CD4 T cell depletion during disease progression to AIDS. ..
  19. ncbi HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment
    Katherine Luzuriaga
    Program in Molecular Medicine Department of Pediatrics Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester
    J Infect Dis 210:1529-38. 2014
    ..Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality...
  20. pmc Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR
    Celina M Abreu
    Departamento de Genetica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 9:e97257. 2014
    ..Although the mechanisms of action of the three ISDs are primarily attributed to the PKC pathway, downregulation of surface receptors and stimulation of the viral LTR might be differentially modulated by different PKC isoforms. ..
  21. ncbi Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay
    Jeremy A Barry
    W M Keck FT Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA
    J Am Soc Mass Spectrom 25:2038-47. 2014
    ..In addition, a targeted MS(2) imaging experiment was also conducted to demonstrate the capabilities of the Q Exactive and to highlight the added selectivity that can be obtained with SRM or MRM imaging experiments. ..
  22. pmc New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo
    C Korin Bullen
    1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2
    Nat Med 20:425-9. 2014
    ..Further, our data indicate that non-activating LRAs are unlikely to drive the elimination of the latent reservoir in vivo when administered individually. ..
  23. pmc Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat
    Julie K Jadlowsky
    Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Mol Cell Biol 34:1911-28. 2014
    ..In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses. ..
  24. pmc HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat
    Nancy M Archin
    Department of Medicine, University of North Carolina at Chapel Hill
    J Infect Dis 210:728-35. 2014
    ..The ability of multiple exposures to VOR to repeatedly disrupt latency has not been directly measured, to our knowledge...
  25. pmc Efficient delivery of lentiviral vectors into resting human CD4 T cells
    X Geng
    Virology and Immunology, J David Gladstone Institutes, San Francisco, CA, USA
    Gene Ther 21:444-9. 2014
    ..This technology can also be extended to primary lymphoid cultures where authentic cellular composition and functional relationships are preserved. ..
  26. pmc Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure
    Uri Mbonye
    Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States
    Virology 454:328-39. 2014
    ..An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir. ..
  27. pmc Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription
    Pingyang Liu
    From the Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143 0703, and
    J Biol Chem 289:9918-25. 2014
    ..Thus, P-TEFb regulates its own equilibrium in cells, most likely to maintain optimal cellular homeostasis. ..
  28. pmc A case cluster demonstrating the relationship between HLA concordance and virologic and disease outcomes in human immunodeficiency virus infection
    A Chaillon
    University of California, San Diego, La Jolla, CA, USA Inserm UMR U966, Tours, France Electronic address
    Virology 449:104-8. 2014
    ..We suggest that non-viral factors, which might be related to differences in the HLA profile, played a role in determining different CD4+ T-cells dynamics for these two recipients. ..
  29. pmc Targeted cytotoxic therapy kills persisting HIV infected cells during ART
    Paul W Denton
    Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
    PLoS Pathog 10:e1003872. 2014
    ..These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. ..
  30. pmc HLA-B*57 elite suppressor and chronic progressor HIV-1 isolates replicate vigorously and cause CD4+ T cell depletion in humanized BLT mice
    Maria Salgado
    Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Virol 88:3340-52. 2014
    ..A better understanding of the immunological bases of viral suppression in ES will serve to inform novel approaches to preventive and therapeutic HIV vaccine design...
  31. pmc An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients
    Celsa A Spina
    Veterans Administration San Diego Healthcare System, San Diego, California, United States of America Department of Pathology, University of California San Diego, La Jolla, California, United States of America
    PLoS Pathog 9:e1003834. 2013
    ..Protein kinase C agonists and PHA reactivated latent HIV uniformly across models, although drugs in most other classes did not. ..
  32. pmc Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
    Gilad Doitsh
    1 Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA 2
    Nature 505:509-14. 2014
    ..This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus. ..
  33. pmc HIV-1 infection of hematopoietic progenitor cells in vivo in humanized mice
    Christopher C Nixon
    Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA
    Blood 122:2195-204. 2013
    ..Further, the nonobese diabetic severe combined immunodeficiency common γ chain knockout-bone marrow-liver-thymus humanized mouse provides a unique model for studying the impact of HIV infection on bone marrow-based human hematopoiesis. ..
  34. pmc HIV-1 clade B pol evolution following primary infection
    George K Hightower
    Department of Medicine, University of California San Diego, La Jolla, California United States of America
    PLoS ONE 8:e68188. 2013
    ..Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals...
  35. pmc Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy
    Tuan Le
    Veterans Affairs Research Center for AIDS and HIV 1 Infection, South Texas Veterans Health Care System, San Antonio, Texas, USA
    N Engl J Med 368:218-30. 2013
    ..The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown...
  36. pmc New assays for monitoring residual HIV burden in effectively treated individuals
    Matthew C Strain
    University of California San Diego, La Jolla, California 92093 0679, USA
    Curr Opin HIV AIDS 8:106-10. 2013
    ..This review summarizes recent advances that may lead to clinically useful tests with improved sensitivity, reproducibility and throughput...
  37. pmc BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism
    Daniela Boehm
    Gladstone Institute of Virology and Immunology, San Francisco, CA, USA
    Cell Cycle 12:452-62. 2013
    ..Collectively, our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency...
  38. pmc Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection
    Erica Weber
    Joint Doctoral Program in Clinical Psychology, San Diego State University and University of California, San Diego, CA 92103, USA
    J Neurovirol 19:65-74. 2013
    ..Extending prior neuroimaging findings, the results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use...
  39. pmc Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells
    Nadejda Beliakova-Bethell
    Department of Medicine, University of California San Diego, La Jolla CA 92093 0679, USA
    AIDS 27:29-37. 2013
    ..To assess the off-target effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells...
  40. pmc Snapshots: chromatin control of viral infection
    David M Knipe
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
    Virology 435:141-56. 2013
    ....
  41. pmc miRNA profiles of monocyte-lineage cells are consistent with complicated roles in HIV-1 restriction
    Jeanne M Sisk
    Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Viruses 4:1844-64. 2012
    ....
  42. pmc Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells
    Sona Budhiraja
    Department of Molecular Microbiology and Virology, Baylor College of Medicine, Houston, TX, USA
    J Virol 87:1211-20. 2013
    ....
  43. pmc Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes
    Brandon S Razooky
    Department of Chemistry and Biochemistry, University of California, San Diego, CA 92023, USA
    Lab Chip 12:4305-12. 2012
    ..The proposed devices offer a simple, robust approach to long-term single-cell studies of environmentally sensitive primary lymphocytes...
  44. pmc Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy
    N M Archin
    The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nature 487:482-5. 2012
    ....
  45. pmc BET bromodomain inhibition as a novel strategy for reactivation of HIV-1
    Camellia Banerjee
    Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Leukoc Biol 92:1147-54. 2012
    ..Thus, JQ1 may be useful in studies of potentially novel mechanisms for transcriptional control as well as in translational efforts to identify therapeutic molecules to achieve viral eradication...
  46. pmc Facts and fiction: cellular models for high throughput screening for HIV-1 reactivating drugs
    Vicente Planelles
    Department of Pathology, University of Utah, Salt Lake City, USA
    Curr HIV Res 9:568-78. 2011
    ..We provide an overview from the first reported latently infected cell lines to current in vitro models of latent HIV-1 infection in primary T cells, and compare their potential to be used in future large-scale drug screening efforts...
  47. pmc Control of HIV latency by epigenetic and non-epigenetic mechanisms
    Uri Mbonye
    Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Curr HIV Res 9:554-67. 2011
    ....
  48. pmc HIV latency in the humanized BLT mouse
    Matthew D Marsden
    Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    J Virol 86:339-47. 2012
    ..Therefore, the HIV-infected BLT mouse should provide a useful model for assessment of HIV latency activators and approaches to eliminate persistent in vivo HIV reservoirs...
  49. pmc Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies
    Susanne Eriksson
    Department of Diagnostics and Vaccinology, Swedish Institute for Communicable Diseases, Solna, Sweden
    PLoS Pathog 9:e1003174. 2013
    ..A molecular understanding of the discrepancy between infected cell frequencies measured by viral outgrowth versus PCR assays is an urgent priority in HIV-1 cure research...
  50. pmc Modulation of BK channel by MicroRNA-9 in neurons after exposure to HIV and methamphetamine
    Erick T Tatro
    Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093 0603, USA
    J Neuroimmune Pharmacol 8:1210-23. 2013
    ..Our results suggest that HIV and MA -induced elevated miR-9, leading to suppression of MRE-containing splice variants of KCNMA1, which may affect neurotransmitter release in dopaminergic neurons. ..
  51. pmc Reactivation of latent HIV by histone deacetylase inhibitors
    Kotaro Shirakawa
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
    Trends Microbiol 21:277-85. 2013
    ..Here, we review the basic biology of HDACs and their inhibitors, the role of HDACs in HIV latency, and recent efforts to use HDAC inhibitors to reactivate latent HIV in vitro and in vivo...
  52. pmc Bromodomain proteins in HIV infection
    Daniela Boehm
    Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
    Viruses 5:1571-86. 2013
    ..We end with an overview of promising new studies of bromodomain inhibitory compounds for the treatment of HIV latency. ..
  53. pmc Cryptopatches are essential for the development of human GALT
    Tomonori Nochi
    Division of Infectious Diseases, Center for AIDS Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Cell Rep 3:1874-84. 2013
    ..This human-mouse chimeric model represents the most comprehensive experimental platform currently available for the study and for the preclinical testing of therapeutics designed to repair disease-damaged GALT...
  54. pmc Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs: limited evidence for general uptake of dietary plant xenomiRs
    Kenneth W Witwer
    Department of Molecular and Comparative Pathobiology The Johns Hopkins University School of Medicine Baltimore, ME USA
    RNA Biol 10:1080-6. 2013
    ....
  55. pmc Antiretroviral pharmacology in mucosal tissues
    Corbin G Thompson
    Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 27599 7569, USA
    J Acquir Immune Defic Syndr 63:S240-7. 2013
    ..Finally, we suggest how preclinical and clinical data might be practically translated into optimal preexposure prophylaxis dosing strategies for clinical trials testing using mathematical modeling and simulation...
  56. pmc Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay
    Gregory M Laird
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    PLoS Pathog 9:e1003398. 2013
    ..The reductions in both labor and cost make this assay suitable for quantifying the frequency of latently infected cells in clinical trials of HIV-1 eradication strategies...
  57. pmc HIV/AIDS eradication
    Matthew D Marsden
    Department of Medicine, Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, CA 90095, USA
    Bioorg Med Chem Lett 23:4003-10. 2013
    ..This latter approach could involve the use of novel chemically synthesized analogs of natural activating agents. ..
  58. pmc HIV-1 eradication strategies: design and assessment
    Janet D Siliciano
    Johns Hopkins University School of Medicine and Howard Hughes Medical Institute, Baltimore, MD 22105, USA
    Curr Opin HIV AIDS 8:318-25. 2013
    ..Recent developments have generated renewed interest in the possibility of curing HIV-1 infection. This review describes some of the practical challenges that will need to be overcome if curative strategies are to be successful...
  59. pmc Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient
    Steven A Yukl
    San Francisco VA Medical Center and University of California, San Francisco, San Francisco, California, United States of America
    PLoS Pathog 9:e1003347. 2013
    ..The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure...
  60. pmc Using ultradeep pyrosequencing to study HIV-1 coreceptor usage in primary and dual infection
    Gabriel A Wagner
    University of California San Diego, La Jolla, CA 92093, USA
    J Infect Dis 208:271-4. 2013
    ..12), suggesting a weak statistical trend toward occurrence of superinfection and acquiring X4 usage...
  61. pmc Highly precise measurement of HIV DNA by droplet digital PCR
    Matthew C Strain
    University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 8:e55943. 2013
    ..The improved sensitivity and precision of measurement of these rare events should facilitate measurements to characterize the latent HIV reservoir and interventions to eradicate it...
  62. pmc How to best measure HIV reservoirs?
    Christine Rouzioux
    Department of Virology, Necker Hospital, Paris Descartes University, Paris Sorbonne Cité, Paris, France
    Curr Opin HIV AIDS 8:170-5. 2013
    ..Measuring HIV reservoirs accurately will be necessary to assess those strategies. The objective of this review is to present the most recent studies that may help to define the best markers to measure HIV reservoirs...
  63. pmc Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs
    Christine Katlama
    Department of Infectious Diseases, Pierre and Marie Curie University, Pitie Salpetriere Hospital, Paris, France
    Lancet 381:2109-17. 2013
    ....
  64. pmc Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription
    Koen Bartholomeeusen
    Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143 0703, USA
    J Biol Chem 288:14400-7. 2013
    ..We conclude that HDACis, which can reactivate HIV, work via the release of free P-TEFb from the 7SK snRNP...
  65. pmc Lost in transcription: molecular mechanisms that control HIV latency
    Ran Taube
    The Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, P O Box 653, Beer Sheva 84105, Israel
    Viruses 5:902-27. 2013
    ....
  66. pmc Generation of HIV latency in humanized BLT mice
    Paul W Denton
    Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina, USA
    J Virol 86:630-4. 2012
    ..These results demonstrate the potential of humanized BLT mice as an attractive model for testing the in vivo efficacy of novel HIV eradication strategies...

Research Grants30

  1. Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases Research
    Alan G Barbour; Fiscal Year: 2013
    ..abstract_text> ..
  2. Mechanisms of immune Failure in Chronic Infection: Hepatitis C as a Key Paradigm
    Raymond T Chung; Fiscal Year: 2013
    ..7. Develop a platform technology to examine and modulate critical signaling pathways that limit the adaptive immune response (TDP/Haining). ..
  3. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  4. Optimizing HIV immunogen-BCR interactions for vaccine development
    LEONIDAS A STAMATATOS; Fiscal Year: 2013
    ....
  5. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  6. Directing Tumor-specific T cells to Tumors
    Pawel Kalinski; Fiscal Year: 2013
    ..abstract_text> ..
  7. Novel Ad/MVA and Ad/Protein HIV-1 Vaccines
    Dan H Barouch; Fiscal Year: 2013
    ..To define the mechanism of blocking acquisition of stringent SIV challenges by conducting antigen formulation and adoptive transfer studies in rhesus monkeys. ..