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https://www.readbyqxmd.com/read/29324463/fractures-related-to-tenofovir-a-case-noncase-study-in-the-european-pharmacovigilance-database
#1
Montserrat G García, Unai Larrinaga-Torrontegui, Eduardo Eduardo Martinez, Unax Lertxundi, Itziar Palacios-Zabalza, Carmelo Aguirre
BACKGROUND: There is no clear consensus on the relationship between tenofovir (TDF) and fracture risk because the studies published so far present contradictory findings. STUDY QUESTION: Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of fracture risk during TDF exposure in patients infected with HIV. METHODS: Herein, we analyze all the cases of fractures suspected to be related to TDF recorded in EudraVigilance between 2001 and November 10, 2016...
January 8, 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29324227/getting-the-kill-into-shock-and-kill-strategies-to-eliminate-latent-hiv
#2
REVIEW
Youry Kim, Jenny L Anderson, Sharon R Lewin
Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29321330/glycosyl-phosphatidylinositol-anchored-anti-hiv-env-single-chain-variable-fragments-interfere-with-hiv-1-env-processing-and-viral-infectivity
#3
Anisha Misra, Emile Gleeson, Weiming Wang, Chaobaihui Ye, Paul Zhou, Jason T Kimata
In previous studies, we demonstrated that single-chain variable fragments (scFv) from anti-HIV Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphitidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with infectivity of newly produced virions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#4
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29305013/transcription-insights-from-the-hiv-1-promoter
#5
Enrico Ne, Robert-Jan Palstra, Tokameh Mahmoudi
In this review, we cover transcription regulation of human immunodeficiency virus type 1 (HIV-1) gene expression, focusing on the invaluable contributions, made by HIV research over the years, toward the field of transcription. In this context, the HIV promoter can be considered to be a well-studied model promoter, which although a viral promoter, is subject to the same cellular regulatory mechanisms that modulate the transcriptional control of endogenous host cellular genes. The molecular control of HIV-1 transcription has been well studied and considerable knowledge toward development of alternative strategies for therapies aimed at eradicating both active but also latent HIV-1 has been obtained...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29298886/class-1-selective-histone-deacetylase-inhibitors-enhance-hiv-latency-reversal-while-preserving-the-activity-of-hdac-isoforms-necessary-for-maximal-hiv-gene-expression
#6
Thomas D Zaikos, Mark M Painter, Nadia T Sebastian, Valeri H Terry, Kathleen L Collins
Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of PKC agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of pro-viral factors regulated by non-class 1 histone deacetylases...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29296946/latent-human-cytomegalovirus-enhances-hiv-1-infection-in-cd34-progenitor-cells
#7
Allen Ka Loon Cheung, Yiru Huang, Hau Yee Kwok, Min Chen, Zhiwei Chen
Individuals who have been preinfected by human cytomegalovirus (HCMV) are more prone to AIDS disease progression after subsequent HIV-1 infection but the underlying mechanism remains elusive. HCMV is a ubiquitous DNA virus that commonly establishes lifelong latent infection in CD34+ progenitor cells, where latency-specific HCMV genes may modulate host restriction to HIV-1 infection. To test this hypothesis, we studied progenitor cells that are known to resist replicative HIV-1 infection because of the intrinsic expression of host restriction factors...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296171/micrornas-sequencing-unveils-distinct-molecular-subgroups-of-plasmablastic-lymphoma
#8
Maria Raffaella Ambrosio, Lucia Mundo, Sara Gazaneo, Matteo Picciolini, Prasad Satya Vara, Shaheen Sayed, Alessandro Ginori, Giuseppe Lo Bello, Leonardo Del Porro, Mohsen Navari, Stefano Ascani, Amhed Yonis, Lorenzo Leoncini, Pier Paolo Piccaluga, Stefano Lazzi
Plasmablastic lymphoma (PBL) is an aggressive lymphoma, often arising in the context of immunodeficiency and associated with Epstein-Barr virus (EBV) infection. The most frequently detected genetic alteration is the deregulation of MYC gene through the translocation - t(8;14)(q24;q32). The diagnosis of PBL is often challenging because it has an overlap in morphology, immunophenotype, cytogenetics and virus association with other lymphomas and plasma cell neoplasms; further, its molecular basis remains elusive...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277280/lymphadenopathies-in-human-immunodeficiency-virus-infection
#9
REVIEW
Carlos Barrionuevo-Cornejo, Daniela Dueñas-Hancco
This article describes the various non-neoplastic lymphadenopathies that occur in patients infected with the human immunodeficiency virus (HIV), before or during the stage of acquired immunodeficiency syndrome (AIDS). The stages that develop during the HIV infection include: primary infection (acute infection, spread of the virus, development of host immune response, and acute retroviral syndrome), chronic infection or clinical latency, and finally, the AIDS stage. Non-neoplastic lymphadenopathies can occur at any of these phases of the infection and are due to multiple causes that can be divided into infectious causes (bacterial, fungal, parasitic, viral), and reactive causes (persistent generalized lymphadenopathy and a variety of situations that they also occur in immunocompetent people such as Castleman's disease and Kikuchi-Fujimoto's disease, among others)...
December 6, 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/29259582/experimental-oral-herpes-simplex-virus-1-hsv-1-co-infection-in-simian-immunodeficiency-virus-siv-infected-rhesus-macaques
#10
Meropi Aravantinou, Olga Mizenina, Giulia Calenda, Jessica Kenney, Ines Frank, Jeffrey D Lifson, Moriah Szpara, Lichen Jing, David M Koelle, Natalia Teleshova, Brooke Grasperge, James Blanchard, Agegnehu Gettie, Elena Martinelli, Nina Derby
Herpes simplex virus 1 and 2 (HSV-1/2) similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV) transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP) models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29246970/compounds-producing-an-effective-combinatorial-regimen-for-disruption-of-hiv-1-latency
#11
Pargol Hashemi, Kris Barreto, Wendy Bernhard, Adam Lomness, Nicolette Honson, Tom A Pfeifer, P Richard Harrigan, Ivan Sadowski
Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compounds that are capable of reversing HIV latency without affecting the general T-cell activation state. The new compounds exhibit synergy for reactivation of latent provirus with other latency-reversing agents (LRAs), in particular ingenol-3-angelate/PEP005...
December 15, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29234320/increasing-the-clinical-potential-and-applications-of-anti-hiv-antibodies
#12
REVIEW
Casey K Hua, Margaret E Ackerman
Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the clinical utility and potential of bNAbs for prevention, postexposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of antidrug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29228979/contrasting-effect-of-the-latency-reversing-agents-bryostatin-1-and-jq1-on-astrocyte-mediated-neuroinflammation-and-brain-neutrophil-invasion
#13
Alizé Proust, Corinne Barat, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
BACKGROUND: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. METHODS: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29228368/the-oncolytic-virus-mg1-targets-and-eliminates-latently-hiv-1-infected-cells-implications-for-an-hiv-cure
#14
Nischal Ranganath, Teslin S Sandstrom, Stephanie C Burke Schinkel, Sandra C Côté, Jonathan B Angel
Latently HIV-infected cells evade immune- and drug-mediated clearance. These cells harbour intracellular signalling defects including impairment of the antiviral, type I IFN (IFN-I) response. Such defects have also been observed in several cancers, and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate latently HIV-1-infected cells, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in latently HIV-1-infected cell lines...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29212213/the-bromodomain-and-extraterminal-domain-inhibitor-bromosporine-synergistically-reactivates-latent-hiv-1-in-latently-infected-cells
#15
Hanyu Pan, Panpan Lu, Yinzhong Shen, Yanan Wang, Zhengtao Jiang, Xinyi Yang, Yangcheng Zhong, He Yang, Inam Ulla Khan, Muya Zhou, Bokang Li, Ziyu Zhang, Jianqing Xu, Hongzhou Lu, Huanzhang Zhu
The long-lived latent HIV-1 reservoir is the major barrier for complete cure of Acquired Immune Deficiency Syndrome (AIDS). Here we report that a novel bromodomain and extraterminal domain (BET) inhibitor bromosporine which can broadly target BETs, is able to potently reactivate HIV-1 replication in different latency models alone and more powerful when combined with prostratin or TNF-α. Furthermore, the treatment with bromosporine induced HIV-1 full-length transcripts in resting CD4+ T cells from infected individuals with suppressive antiretroviral therapy (ART) ex vivo, with no obvious cytotoxicity or global activation of T cell...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210645/editorial-acting-on-tat-mediated-transcription-to-achieve-a-long-term-control-of-hiv-1-latency
#16
EDITORIAL
Oriana Tabarrini, Serena Massari
No abstract text is available yet for this article.
November 2, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29207194/quercetin-synergistically-reactivates-human-immunodeficiency-virus-type-1-latency-by-activating-nuclear-factor%C3%A2-%C3%AE%C2%BAb
#17
Xinyi Yang, Xiaoli Zhu, Haiyan Ji, Junxiao Deng, Panpan Lu, Zhengtao Jiang, Xian Li, Yibo Wang, Chuqiao Wang, Jingya Zhao, Yanan Wang, Yangcheng Zhong, He Yang, Huanzhang Zhu
Highly active antiretroviral therapy (HAART) is very effective in suppressing human immunodeficiency virus type 1 (HIV‑1) replication. However, the treatment is required to be administered for the remainder of an individual's lifetime due to latent HIV‑1 reservoirs. The 'shock‑and‑kill' strategy, which involves using agents to reactivate latent HIV‑1 and subsequently killing latently infected cells in the presence of HAART, was recently proposed. Unfortunately, no agents have currently demonstrated an ability to reactivate latent HIV‑1 in vivo in the absence of toxicity...
November 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206656/hiv-integration-sites-and-implications-for-maintenance-of-the-reservoir
#18
Jori Symons, Paul U Cameron, Sharon R Lewin
PURPOSE OF REVIEW: To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. RECENT FINDINGS: How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear...
December 4, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29196729/peripheral-t-follicular-helper-cells-make-a-difference-in-hiv-reservoir-size-between-elite-controllers-and-patients-on-successful-cart
#19
Marcial García, Miguel Górgolas, Alfonso Cabello, Vicente Estrada, José Manuel Ligos, Manuel Fernández-Guerrero, Carlos Barros, Juan Carlos López-Bernaldo, Francisco Javier De La Hera, María Montoya, José Miguel Benito, Norma Rallón
HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29192235/multiplex-single-cell-visualization-of-nucleic-acids-and-protein-during-hiv-infection
#20
Maritza Puray-Chavez, Philip R Tedbury, Andrew D Huber, Obiaara B Ukah, Vincent Yapo, Dandan Liu, Juan Ji, Jennifer J Wolf, Alan N Engelman, Stefan G Sarafianos
Technical limitations in simultaneous microscopic visualization of RNA, DNA, and proteins of HIV have curtailed progress in this field. To address this need we develop a microscopy approach, multiplex immunofluorescent cell-based detection of DNA, RNA and Protein (MICDDRP), which is based on branched DNA in situ hybridization technology. MICDDRP enables simultaneous single-cell visualization of HIV (a) spliced and unspliced RNA, (b) cytoplasmic and nuclear DNA, and (c) Gag. We use MICDDRP to visualize incoming capsid cores containing RNA and/or nascent DNA and follow reverse transcription kinetics...
December 1, 2017: Nature Communications
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