Martin Delaney Collaboratory to Eradicate HIV-1 Infection
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
- Screening for noise in gene expression identifies drug synergiesRoy 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. ..
- Emerging strategies to deplete the HIV reservoirNancie 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...
- Real-world impact of neurocognitive deficits in acute and early HIV infectionKatie 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....
- Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United StatesGabriel 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)...
- Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cureYa 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...
- An integrated overview of HIV-1 latencyDebbie 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. ..
- Antibody response to Achromobacter xylosoxidans during HIV infection is associated with lower CD4 levels and increased lymphocyte activationErick 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. ..
- HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) modelJenna 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...
- Reactivation of latent HIV-1 in central memory CD4⁺ T cells through TLR-1/2 stimulationCamille 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...
- Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivationAlexandra Duverger
Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
J Virol 88:364-76. 2014....
- Absence of detectable HIV-1 viremia after treatment cessation in an infantDeborah 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. ..
- The effect of cell subset isolation method on gene expression in leukocytesNadejda 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...
- Tristetraprolin expression and microRNA-mediated regulation during simian immunodeficiency virus infection of the central nervous systemJonathan 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...
- SIV replication is directly downregulated by four antiviral miRNAsJeanne 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...
- HIV latency and integration site placement in five cell-based modelsScott Sherrill-Mix
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Retrovirology 10:90. 2013....
- Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitorsMary 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. ..
- A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapyAdam 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...
- IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIVKathryn 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. ..
- HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatmentKatherine 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...
- Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTRCelina 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. ..
- Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM AssayJeremy 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. ..
- New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivoC 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. ..
- 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 repeatJulie 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. ..
- HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostatNancy 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...
- Efficient delivery of lentiviral vectors into resting human CD4 T cellsX 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. ..
- Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cureUri 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. ..
- Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcriptionPingyang 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. ..
- A case cluster demonstrating the relationship between HLA concordance and virologic and disease outcomes in human immunodeficiency virus infectionA 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. ..
- Targeted cytotoxic therapy kills persisting HIV infected cells during ARTPaul 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. ..
- HLA-B*57 elite suppressor and chronic progressor HIV-1 isolates replicate vigorously and cause CD4+ T cell depletion in humanized BLT miceMaria 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...
- An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patientsCelsa 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. ..
- Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infectionGilad 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. ..
- HIV-1 infection of hematopoietic progenitor cells in vivo in humanized miceChristopher 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. ..
- HIV-1 clade B pol evolution following primary infectionGeorge 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...
- Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapyTuan 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...
- New assays for monitoring residual HIV burden in effectively treated individualsMatthew 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...
- BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanismDaniela 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...
- Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infectionErica 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...
- Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cellsNadejda 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...
- Snapshots: chromatin control of viral infectionDavid M Knipe
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
Virology 435:141-56. 2013....
- miRNA profiles of monocyte-lineage cells are consistent with complicated roles in HIV-1 restrictionJeanne M Sisk
Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Viruses 4:1844-64. 2012....
- Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cellsSona Budhiraja
Department of Molecular Microbiology and Virology, Baylor College of Medicine, Houston, TX, USA
J Virol 87:1211-20. 2013....
- Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytesBrandon 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...
- Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapyN M Archin
The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Nature 487:482-5. 2012....
- BET bromodomain inhibition as a novel strategy for reactivation of HIV-1Camellia 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...
- Facts and fiction: cellular models for high throughput screening for HIV-1 reactivating drugsVicente 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...
- Control of HIV latency by epigenetic and non-epigenetic mechanismsUri Mbonye
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
Curr HIV Res 9:554-67. 2011....
- HIV latency in the humanized BLT mouseMatthew 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...
- Comparative analysis of measures of viral reservoirs in HIV-1 eradication studiesSusanne 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...
- Modulation of BK channel by MicroRNA-9 in neurons after exposure to HIV and methamphetamineErick 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. ..
- Reactivation of latent HIV by histone deacetylase inhibitorsKotaro 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...
- Bromodomain proteins in HIV infectionDaniela 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. ..
- Cryptopatches are essential for the development of human GALTTomonori 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...
- 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 xenomiRsKenneth W Witwer
Department of Molecular and Comparative Pathobiology The Johns Hopkins University School of Medicine Baltimore, ME USA
RNA Biol 10:1080-6. 2013....
- Antiretroviral pharmacology in mucosal tissuesCorbin 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...
- Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assayGregory 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...
- HIV/AIDS eradicationMatthew 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. ..
- HIV-1 eradication strategies: design and assessmentJanet 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...
- Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patientSteven 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...
- Using ultradeep pyrosequencing to study HIV-1 coreceptor usage in primary and dual infectionGabriel 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...
- Highly precise measurement of HIV DNA by droplet digital PCRMatthew 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...
- 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...
- Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirsChristine Katlama
Department of Infectious Diseases, Pierre and Marie Curie University, Pitie Salpetriere Hospital, Paris, France
Lancet 381:2109-17. 2013....
- Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcriptionKoen 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...
- Lost in transcription: molecular mechanisms that control HIV latencyRan 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....
- Generation of HIV latency in humanized BLT micePaul 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...
- Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases ResearchAlan G Barbour; Fiscal Year: 2013..abstract_text> ..
- Mechanisms of immune Failure in Chronic Infection: Hepatitis C as a Key ParadigmRaymond 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). ..
- 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. ..
- Optimizing HIV immunogen-BCR interactions for vaccine developmentLEONIDAS A STAMATATOS; Fiscal Year: 2013....
- Rocky Mountain Regional Center of Excellence or Biodefense and Emerging InfectiouJohn T Belisle; Fiscal Year: 2013..abstract_text> ..
- Directing Tumor-specific T cells to TumorsPawel Kalinski; Fiscal Year: 2013..abstract_text> ..
- Novel Ad/MVA and Ad/Protein HIV-1 VaccinesDan 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. ..