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https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#1
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28729655/a-crispr-cas9-guidance-rna-screen-platform-for-hiv-provirus-disruption-and-hiv-aids-gene-therapy-in-astrocytes
#2
Zaohua Huang, Madahavan Nair
HIV/AIDS remains a major health threat despite significant advances in the prevention and treatment of HIV infection. The major reason is the inability of existing treatments to eradicate the multiple HIV reservoirs in the human body, including astrocytes in the human brain. CRISPR/Cas9 system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a complete cure of HIV/AIDS. The key components of CRISPR/Cas9 are guide RNAs (gRNAs) which determine specific sequence targeting of DNAs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#3
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28720421/assessment-of-the-hiv-1-reservoir-in-cd4-regulatory-t-cells-by-a-droplet-digital-pcr-based-approach
#4
Gábor Artúr Dunay, Anastasia Solomatina, Silke Kummer, Anja Hüfner, Julia Katharina Bialek, Johanna Maria Eberhard, Eva Tolosa, Joachim Hauber, Julian Schulze Zur Wiesch
The relative contribution of regulatory T cells (Treg) as reservoir of HIV-1 in patients on chronic antiretroviral therapy is unclear to date. The aim of the current study was to assess the total HIV DNA burden and replication competent viral reservoir in Treg in comparison to central and effector memory cells (Tcm and Tem). Peripheral blood mononuclear cells were obtained from 10 HIV patients treated with antiretroviral therapy and one HIV elite controller. Droplet Digital PCR (ddPCR) was used to quantify total HIV DNA loads in FACS sorted CD4+ Treg (CD25+CD127lo) as compared with Tcm (CD45RO+CCR7+) and Tem (CD45RO+CCR7-)...
July 15, 2017: Virus Research
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#5
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28715973/the-molecular-basis-for-human-immunodeficiency-virus-latency
#6
Uri Mbonye, Jonathan Karn
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4(+) T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment...
July 17, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28715460/early-infant-diagnosis-of-hiv-1-infection-in-luanda-angola-using-a-new-dna-pcr-assay-and-dried-blood-spots
#7
Francisco Martin, Claudia Palladino, Rita Mateus, Anna Bolzan, Perpétua Gomes, José Brito, Ana Patrícia Carvalho, Yolanda Cardoso, Cristovão Domingos, Vanda Sofia Lôa Clemente, Nuno Taveira
BACKGROUND: Early diagnosis and treatment reduces HIV-1-related mortality, morbidity and size of viral reservoirs in infants infected perinatally. Commercial molecular tests enable the early diagnosis of infection in infants but the high cost and low sensitivity with dried blood spots (DBS) limit their use in sub-Saharan Africa. OBJECTIVES: To develop and validate a sensitive and cheap qualitative proviral DNA PCR-based assay for early infant diagnosis (EID) in HIV-1-exposed infants using DBS samples...
2017: PloS One
https://www.readbyqxmd.com/read/28712302/overcoming-the-hydrolytic-lability-of-a-reaction-intermediate-in-production-of-protein-drug-conjugates-conjugation-of-an-acyclic-nucleoside-phosphonate-to-a-model-carrier-protein
#8
Shengsheng Xu, Igor A Kaltashov
Acquired immunodeficiency syndrome (AIDS) remains one of the most serious public health challenges and a significant cause of mortality for certain populations. Despite the large number of antiretrovirals developed in the past two decades, the inability of small molecule therapeutics to target HIV reservoirs directly creates a significant obstacle to their effective utilization. Indeed, achieving the desired therapeutic outcome in the absence of an effective means of targeted delivery must rely on dosage escalation, which frequently causes severe toxicity...
July 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28708873/impact-of-early-cart-on-hiv-blood-and-semen-compartments-at-the-time-of-primary-infection
#9
Antoine Chéret, Christine Durier, Adeline Mélard, Mickaël Ploquin, Julia Heitzmann, Camille Lécuroux, Véronique Avettand-Fenoël, Ludivine David, Gilles Pialoux, Jean-Marie Chennebault, Michaela Müller-Trutwin, Cécile Goujard, Christine Rouzioux, Laurence Meyer
BACKGROUND: HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. METHODS: Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28701422/new-highly-sensitive-real-time-pcr-assay-for-hiv-2-group-a-and-group-b-dna-quantification
#10
Mélanie Bertine, Marie Gueudin, Adeline Mélard, Florence Damond, Diane Descamps, Sophie Matheron, Fidéline Collin, Christine Rouzioux, Jean-Christophe Plantier, Véronique Avettand-Fenoel
HIV-2 infection is characterized by a very low replication in most cases and low progression. That necessitates a different approach to patient monitoring than that for HIV-1 infection. Here, a new, highly specific, and sensitive method for HIV-2 DNA quantification has been developed. The new test is based on quantitative real-time PCR, targeting the LTR and Gag regions and using an internal control. Analytical performance was determined in three laboratories and clinical performance on blood samples from 63 patients infected with HIV-2 group A (n=35) or group B (n=28)...
July 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28698276/a-novel-single-cell-fish-flow-assay-identifies-effector-memory-cd4-t-cells-as-a-major-niche-for-hiv-1-transcription-in-hiv-infected-patients
#11
Judith Grau-Expósito, Carla Serra-Peinado, Lucia Miguel, Jordi Navarro, Adrià Curran, Joaquin Burgos, Imma Ocaña, Esteban Ribera, Ariadna Torrella, Bibiana Planas, Rosa Badía, Josep Castellví, Vicenç Falcó, Manuel Crespo, Maria J Buzon
Cells that actively transcribe HIV-1 have been defined as the "active viral reservoir" in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence in situ hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4(+) T cells...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28693065/-advances-in-clinical-research-of-dna-reservoir-in-hiv-infected-patients
#12
(no author information available yet)
No abstract text is available yet for this article.
July 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28692537/early-initiation-of-antiretroviral-treatment-post-siv-infection-does-not-resolve-lymphoid-tissue-activation
#13
Jung Joo Hong, Eduardo L V Silveira, Praveen K Amancha, Siddappa N Byrareddy, Sanjeev Gumber, Kyu-Tae Chang, Aftab A Ansari, Francois Villinger
OBJECTIVE: Germinal center (GC) resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/SIV replication. But the dynamics of GCs upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post SIV infection are not fully understood. DESIGN: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks post infection/pre ART, 6 and 12 weeks following ART initiation...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28692305/fight-fire-with-fire-gene-therapy-strategies-to-cure-hiv
#14
Jon Huyghe, Sips Magdalena, Linos Vandekerckhove
Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART...
July 14, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28691499/eradication-of-hiv-from-tissue-reservoirs-challenges-for-the-cure
#15
Rebecca R Rose, David J Nolan, Ekaterina Maidji, Cheryl Stoddart, Elyse J Singer, Susanna Lamers, Michael McGrath
The persistence of Human Immunodeficiency Virus (HIV) infection, even after lengthy and successful combined anti-retroviral therapy (cART), has precluded an effective cure. The anatomical locations in which and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T-cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. Here, we review research supporting the importance of tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages...
July 9, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28691435/clinical-and-public-health-implications-of-acute-and-early-hiv-detection-and-treatment-a-scoping-review
#16
Sarah E Rutstein, Jintanat Ananworanich, Sarah Fidler, Cheryl Johnson, Eduard J Sanders, Omar Sued, Asier Saez-Cirion, Christopher D Pilcher, Christophe Fraser, Myron S Cohen, Marco Vitoria, Meg Doherty, Joseph D Tucker
INTRODUCTION: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. METHODS: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications...
June 28, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28689087/the-histone-deacetylase-inhibitor-saha-simultaneously-reactivates-hiv-1-from-latency-and-up-regulates-nkg2d-ligands-sensitizing-for-natural-killer-cell-cytotoxicity
#17
Maria Giovanna Desimio, Erica Giuliani, Margherita Doria
In pilot HIV-1 eradication studies, patients' immune responses were ineffective at killing viral reservoirs reactivated through latency reversing agents (LRAs) like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using latently HIV-1-infected J-Lat 6.3/8.4/9...
July 6, 2017: Virology
https://www.readbyqxmd.com/read/28687465/on-the-way-to-find-a-cure-purging-latent-hiv-1-reservoirs
#18
REVIEW
Christian Schwartz, Sophie Bouchat, Céline Marban, Virginie Gautier, Carine Van Lint, Olivier Rohr, Valentin Le Douce
Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill)...
July 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28685417/the-lymph-node-in-hiv-pathogenesis
#19
REVIEW
Yiannis Dimopoulos, Eirini Moysi, Constantinos Petrovas
Lymph nodes play a central role in the development of adaptive immunity against pathogens and particularly the generation of antigen-specific B cell responses in specialized areas called germinal centers (GCs). Lymph node (LN) pathology was recognized as an important consequence of human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. Investigation into the structural and functional alterations induced by HIV and Simian immunodeficiency virus (SIV) has further cemented the central role that lymphoid tissue plays in HIV/SIV pathogenesis...
July 7, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28683094/correction-real-time-predictions-of-reservoir-size-and-rebound-time-during-antiretroviral-therapy-interruption-trials-for-hiv
#20
Alison L Hill, Daniel I S Rosenbloom, Edward Goldstein, Emily Hanhauser, Daniel R Kuritzkes, Robert F Siliciano, Timothy J Henrich
[This corrects the article DOI: 10.1371/journal.ppat.1005535.].
July 2017: PLoS Pathogens
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