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https://www.readbyqxmd.com/read/29789664/the-bet-bromodomain-inhibitor-apabetalone-induces-apoptosis-of-latent-hiv-1-reservoir-cells-following-viral-reactivation
#1
Xuan-Xuan Zhang, Jian Lin, Tai-Zhen Liang, Heng Duan, Xing-Hua Tan, Bao-Min Xi, Lin Li, Shu-Wen Liu
The persistence of latent HIV-1 reservoirs throughout combination antiretroviral therapy (cART) is a major barrier on the path to achieving a cure for AIDS. It has been shown that bromodomain and extra-terminal (BET) inhibitors could reactivate HIV-1 latency, but restrained from clinical application due to their toxicity and side effects. Thus, identifying a new type of BET inhibitor with high degrees of selectivity and safety is urgently needed. Apabetalone is a small-molecule selective BET inhibitor specific for second bromodomains, and has been evaluated in phase III clinical trials that enrolled patients with high-risk cardiovascular disorders, dyslipidemia, and low HDL cholesterol...
May 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29781356/combating-the-hiv-reservoirs
#2
Guido van Marle, Deirdre L Church, Frank van der Meer, M John Gill
Impressive advances have been made in the treatment and management of HIV-1 infected individuals. Combination antiretroviral therapy (cART) has turned HIV-1 infection from an almost invariable deadly infectious disease, to a lifelong manageable infectious disease. However, a cure or vaccine has not been forthcoming. A major problem in HIV-1 infection is the persistent and latently infected cellular and tissue reservoirs. One of these reservoirs is the Gut Associated Lymphoid tissue (GALT), which has been the research focus of our group...
May 21, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29780387/cd32-expressing-cd4-t-cells-are-phenotypically-diverse-and-can-contain-proviral-hiv-dna
#3
Genevieve E Martin, Matthew Pace, John P Thornhill, Chansavath Phetsouphanh, Jodi Meyerowitz, Morgane Gossez, Helen Brown, Natalia Olejniczak, Julianne Lwanga, Gita Ramjee, Pontiano Kaleebu, Kholoud Porter, Christian B Willberg, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+ CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low , CD32+ CD14+ , and CD32high ). Of note, CD4 negative enrichment kits remove the majority of CD4+ CD32+ T cells, potentially skewing subsequent analyses if used...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29770863/siv-latency-in-macrophages-in-the-cns
#4
Lucio Gama, Celina Abreu, Erin N Shirk, Suzanne E Queen, Sarah E Beck, Kelly A Metcalf Pate, Brandon T Bullock, M Christine Zink, Joseph L Mankowski, Janice E Clements
Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted...
May 17, 2018: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29769442/distinct-biomarker-signatures-in-hiv-acute-infection-associate-with-viral-dynamics-and-reservoir-size
#5
Jeffrey E Teigler, Louise Leyre, Nicolas Chomont, Bonnie Slike, Ningbo Jian, Michael A Eller, Nittaya Phanuphak, Eugène Kroon, Suteeraporn Pinyakorn, Leigh Anne Eller, Merlin L Robb, Jintanat Ananworanich, Nelson L Michael, Hendrik Streeck, Shelly J Krebs
Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768175/targeting-the-latent-reservoir-for-hiv-1
#6
REVIEW
Srona Sengupta, Robert F Siliciano
Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29762173/a-defucosylated-bispecific-multivalent-molecule-exhibits-broad-hiv-1-neutralizing-activity-and-enhanced-adcc-against-reactivated-hiv-1-latently-infected-cells
#7
Desheng Kong, Yan Wang, Ping Ji, Wei Li, Tianlei Ying, Jinghe Huang, Chen Wang, Yanling Wu, Yanping Wang, Weizao Chen, Yanling Hao, Kunxue Hong, Yiming Shao, Dimiter S Dimitrov, Shibo Jiang, Liying Ma
OBJECTIVE: Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29762162/genetic-characterization-of-the-hiv-1-reservoir-after-vacc-4x-and-romidepsin-therapy-in-hiv-1-infected-individuals
#8
Anni Winckelmann, Vincent Morcilla, Wei Shao, Mariane H Schleimann, Jesper F Højen, Timothy E Schlub, Paul W Denton, Lars Østergaard, Ole S Søgaard, Martin Tolstrup, Sarah Palmer
OBJECTIVE: Therapeutic HIV-1 immunization followed by latency reversal has been suggested as a strategy to eradicate HIV-1. Here we investigate the phylogenetic composition of the HIV-1 regions targeted by the therapeutic HIV-1 peptide vaccine Vacc-4x in participants in a clinical trial. DESIGN: Seventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of Vacc-4x followed by three doses of romidepsin. Seven study participants were selected for sequencing analysis...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29760177/epigenetic-promoter-dna-methylation-of-mir-124-promotes-hiv-1-tat-mediated-microglial-activation-via-mecp2-stat3-axis
#9
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B that were also accompanied by increased global DNA methylation...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29757986/medicinal-plants-used-in-the-treatment-of-human-immunodeficiency-virus
#10
REVIEW
Bahare Salehi, Nanjangud V Anil Kumar, Bilge Şener, Mehdi Sharifi-Rad, Mehtap Kılıç, Gail B Mahady, Sanja Vlaisavljevic, Marcello Iriti, Farzad Kobarfard, William N Setzer, Seyed Abdulmajid Ayatollahi, Athar Ata, Javad Sharifi-Rad
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29746496/pharyngeal-colonization-and-drug-resistance-profiles-of-morraxella-catarrrhalis-streptococcus-pneumoniae-staphylococcus-aureus-and-haemophilus-influenzae-among-hiv-infected-children-attending-art-clinic-of-felegehiwot-referral-hospital-ethiopia
#11
Wondemagegn Mulu, Endalew Yizengaw, Megbaru Alemu, Daniel Mekonnen, Derese Hailu, Kassaw Ketemaw, Bayeh Abera, Mulugeta Kibret
BACKGROUND: Asymptomatic pharyngeal colonization by potential bacteria is the primary reservoir for bacterial species within a population and is considered a prerequisite for development of major childhood diseases such as sinusitis, otitis media, pneumonia, bacteremia, and meningitis. However, there is dearth of data on the colonization and drug resistance pattern of the main bacterial pathogens in the pharynx of HIV infected children in Ethiopia. Therefore, this study determined the pharyngeal colonization and drug resistance profile of bacterial pathogens in HIV infected children attending ART clinic of Felegehiwot Referral Hospital (FHRH), Amhara Region, Ethiopia...
2018: PloS One
https://www.readbyqxmd.com/read/29744964/peering-into-the-hiv-reservoir
#12
REVIEW
Marcial García, María J Buzón, José M Benito, Norma Rallón
The main obstacle to HIV eradication is the establishment of a long-term persistent HIV reservoir. Although several therapeutic approaches have been developed to reduce and eventually eliminate the HIV reservoir, only a few have achieved promising results. A better knowledge of the mechanisms involved in the establishment and maintenance of HIV reservoir is of utmost relevance for the design of new therapeutic strategies aimed at purging it with the ultimate goal of achieving HIV eradication or alternatively a functional cure...
May 9, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29742434/live-imaging-of-hiv-1-transfer-across-t-cell-virological-synapse-to-epithelial-cells-that-promotes-stromal-macrophage-infection
#13
Fernando Real, Alexis Sennepin, Yonatan Ganor, Alain Schmitt, Morgane Bomsel
During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4+ T cells and the epithelial cell mucosal surface...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29739699/early-antiretroviral-therapy-in-hiv-infected-infants-can-it-lead-to-hiv-remission
#14
REVIEW
Stephanie Shiau, Elaine J Abrams, Stephen M Arpadi, Louise Kuhn
Interventions to prevent mother-to-child HIV transmission have been extremely successful, but new HIV infections continue to occur in infants. Strong evidence indicates that combination antiretroviral therapy (ART) for treatment should be started in HIV-infected infants to prevent early morbidity and mortality. In 2013, the report of the Mississippi baby, who was started on ART within 30 h of life and maintained off-treatment remission for 27 months before HIV was once again detectable, generated renewed interest in very early ART initiation...
May 2018: Lancet HIV
https://www.readbyqxmd.com/read/29733244/novel-dna-aptamers-against-ccl21-protein-characterization-and-biomedical-applications-for-targeted-drug-delivery-to-t-cell-rich-zones
#15
Louis Chonco, Gerónimo Fernández, Rahul Kalhapure, María J Hernáiz, Cecilia García-Oliva, Victor M Gonzalez, M Elena Martín, Thirumala Govender, Raveen Parboosing
The chemokine (C-C motif) ligand 21 (CCL21) is a cytokine that attracts CCR7-positive cells to the T cell (paracortical) zone of lymph nodes by directional migration of these cells along the CCL21 gradient. In this article, we sought to mimic this chemotactic mechanism, by identifying a novel aptamer that binds CCL21 with high affinity. In vitro selection of DNA aptamers was performed by the Systematic Evolution of Ligands by Exponential Enrichment. Quantitative polymerase chain reaction (qPCR) and enzyme-linked oligonucleotide assay were used to screen for high-affinity aptamers against human and mouse CCL21 protein, respectively...
May 7, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29727296/croi-2018-advances-in-antiretroviral-therapy
#16
Hong-Van Tieu, Barbara S Taylor, Joyce Jones, Timothy J Wilkin
The 2018 Conference on Retroviruses and Opportunistic Infections (CROI) showcased exciting data on new investigational agents including MK-8591 and tri-specific antibody targeting 3 highly conserved epitopes on HIV-1 in a single antibody. Clinical trials of initial antiretroviral therapy (ART) and switch studies involving bictegravir/emtricitabine/tenofovir alafenamide were presented. Intensification of initial ART with integrase strand transfer inhibitors did not increase the risk of immune reconstitution inflammatory syndrome...
May 2018: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/29725337/humanized-mice-engrafted-with-human-hsc-only-or-hsc-and-thymus-support-comparable-hiv-1-replication-immunopathology-and-responses-to-art-and-immune-therapy
#17
Liang Cheng, Jianping Ma, Guangming Li, Lishan Su
Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2-/- /γc -/- (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29725333/follicular-dendritic-cells-of-lymph-nodes-as-human-immunodeficiency-virus-simian-immunodeficiency-virus-reservoirs-and-insights-on-cervical-lymph-node
#18
REVIEW
Rajnish S Dave, Pooja Jain, Siddappa N Byrareddy
A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29725327/lymph-node-cellular-and-viral-dynamics-in-natural-hosts-and-impact-for-hiv-cure-strategies
#19
REVIEW
Nicolas Huot, Steven E Bosinger, Mirko Paiardini, R Keith Reeves, Michaela Müller-Trutwin
Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29720521/short-term-pifn-%C3%AE-2a-treatment-does-not-significantly-reduce-the-viral-reservoir-of-siv-infected-art-treated-rhesus-macaques
#20
David Palesch, Steven E Bosinger, Maud Mavigner, James M Billingsley, Cameron Mattingly, Diane Carnathan, Mirko Paiardini, Ann Chahroudi, Thomas Vanderford, Guido Silvestri
The major obstacle to HIV-1 eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (ART) and causes rapid viral rebound if treatment is interrupted. Type I interferons are immunomodulatory cytokines that induce antiviral factors and have been evaluated for the treatment of HIV-infected individuals, resulting in moderate reduction of viremia and inconclusive data about their effect on reservoir size. Here, we assessed the potential of pegylated IFN-α2a (pIFN-α2a) to reduce the viral reservoir in SIV-infected, ART-treated rhesus macaques (RMs)...
May 2, 2018: Journal of Virology
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