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HIV gene therapy

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https://www.readbyqxmd.com/read/28639194/rnaa-induced-by-tata-box-targeting-micrornas
#1
Yijun Zhang, Hui Zhang
Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4(+) T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28628034/clonal-expansion-of-genome-intact-hiv-1-in-functionally-polarized-th1-cd4-t-cells
#2
Guinevere Q Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D Walker, Eric S Rosenberg, Xu G Yu, Mathias Lichterfeld
HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28624214/further-characterization-of-the-bifunctional-hiv-entry-inhibitor-scd4-fit45
#3
Alexander Falkenhagen, Sadhna Joshi
HIV entry into target cells is a highly sequential and time-sensitive process. In recent years, potent HIV Env-targeting antibodies, such as VRC01, have been identified. However, antibodies bind only to a single epitope, and mutations that confer resistance to antibody-mediated inhibition of HIV entry have been detected. In contrast, HIV cannot escape from binding to soluble CD4 (sCD4) without a fitness disadvantage. sCD4 has the unique ability to induce conformational changes within the HIV envelope glycoproteins (Env) that allow fusion inhibitors to bind...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622951/population-approach-to-efavirenz-therapy
#4
Hélder Duarte, João Paulo Cruz, Natália Aniceto, Ana Clara Ribeiro, Ana Fernandes, Paulo Paixão, Francisco Antunes, José Morais
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor commonly used as first line therapy in the treatment of human immunodeficiency virus, with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady state plasma concentrations, a population pharmacokinetic model was developed form 96 HIV positive individuals, using a nonlinear mixed effect method with Monolix® software...
June 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#5
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#6
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28609402/hiv-associated-kaposi-sarcoma-and-related-diseases
#7
Priscila H Gonçalves, Thomas S Uldrick, Robert Yarchoan
The search for the etiologic agent for Kaposi sarcoma (KS) led to the discovery of Kaposi sarcoma associated herpesvirus (KSHV) in 1994. KSHV, also called human herpesvirus-8 (HHV-8) has since been shown to be the etiologic agent for several other tumors and diseases, including primary effusion lymphoma (PEL), an extracavitary variant of PEL, KSHV-associated diffuse large B-cell lymphoma, a form of multicentric Castleman disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). KSHV encodes several genes that interfere with innate and specific immunity, thwart apoptosis, enhance cell proliferation and cytokine production, and promote angiogenesis, and these play important roles in the disease pathogenesis...
June 12, 2017: AIDS
https://www.readbyqxmd.com/read/28592757/hiv-negative-plasmablastic-lymphoma-attaining-sustained-remission-with-bortezomib-combined-dose-adjusted-epoch-therapy
#8
Hiroyuki Kobayashi, Norito Miyagi
A 61-year-old, HIV-negative, immunocompetent woman was admitted to our hospital for significant weight loss, painful swelling of her right cheek, and rapid growth of a tumor in the right hard palate. A CT scan revealed a neoplastic lesion in the right maxillary sinus, extending to the surrounding soft bone tissue and oral cavity, as well as multiple osteolytic lesions in the skull. A pathologic examination revealed that the neoplastic cells in the oral cavity were plasmablasts tending to appear as differentiated plasma cells...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28590331/multimodal-analysis-of-drug-transporter-expression-in-gastrointestinal-tissue
#9
Corbin G Thompson, John K Fallon, Michelle Mathews, Paige Charlins, Leila Mulder, Martina Kovarova, Lourdes Adamson, Nithya Srinivas, Amanda Schauer, Craig Sykes, Paul Luciw, J Victor Garcia, Ramesh Akkina, Philip C Smith, Angela D M Kashuba
OBJECTIVES: Drug transporters affect ART tissue disposition, but quantitative measures of drug transporter protein expression across pre-clinical species are not available. Our objective was to use proteomics to obtain absolute transporter concentrations and assess agreement with corresponding gene and immunometric protein data. DESIGN: In order to make interspecies comparisons, two humanized mouse (hu-HSC-Rag (n = 41); BLT (n = 13)) and one primate (rhesus macaque, (NHP, n = 12)) models were dosed to steady-state with combination ART...
June 5, 2017: AIDS
https://www.readbyqxmd.com/read/28589513/prevalence-of-hiv-1-transmitted-drug-resistance-in-recently-infected-treatment-na%C3%A3-ve-persons-in-the-southwest-of-iran-2014-2015
#10
Shokouh Ghafari, Arash Memarnejadian, Alireza Samarbaf-Zadeh, Ehsan Mostafavi, Manoochehr Makvandi, Shokrolah Salmanzadeh, Ata Ghadiri, Michael R Jordan, Elham Mousavi, Fatemeh Jahanbakhsh, Kayhan Azadmanesh
The emergence and transmission of drug resistant HIV mutants is a major concern, especially in resource-limited countries with expanding antiretroviral therapy. Studies have recently reported the prevalence of HIV-1 transmitted drug resistance (TDR) mutations in certain Iranian cities; however, no information is currently available about the level of TDR, as well as the nature of the circulating HIV-1 subtypes, in the Southwestern bordering province of Iran, Khuzestan. Herein, we used a WHO-recommended TDR survey method to classify the prevalence of TDR in indigenous people of Khuzestan province...
June 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28584150/upregulation-of-apoptosis-pathway-genes-in-peripheral-blood-mononuclear-cells-of-hiv-infected-individuals-with-antiretroviral-therapy-associated-mitochondrial-toxicity
#11
Yram Foli, Musie Ghebremichael, Min Li, Elijah Paintsil
A case-control study of the effect of antiretroviral therapy (ART) on apoptosis pathway genes; cases (N=16, HIV-infected with mitochondrial toxicity) and controls (N=16, HIV-uninfected). 26 of 84 genes of the apoptosis pathway were differentially expressed. Two genes, DFFA and TNFRSF1A, classified 75% of study participants correctly into either cases or controls. Thus apoptosis may be in the causal pathway of ART-associated mitochondrial toxicity. These two genes could be markers for detecting and monitoring ART-induced mitochondrial toxicity...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28583112/clinical-and-genetic-factors-associated-with-kidney-tubular-dysfunction-in-a-real-life-single-centre-cohort-of-hiv-positive-patients
#12
S E Salvaggio, A Giacomelli, F S Falvella, M L Oreni, P Meraviglia, C Atzori, E G I Clementi, M Galli, S Rusconi
BACKGROUND: Tenofovir (TDF) is one of the most widely used antiretroviral drug. Despite the high degree of tolerability a small percentage of patients experienced alteration in tubular function during TDF use. Intracellular TDF disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters and, a reduced transport activity may be implicated in accumulation of TDF into the cells. The aim of our study was to assess the major determinants of TDF associated tubular dysfunction (KTD) in a real-life setting including the usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4 and ABCC10 genes...
June 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28579286/hiv-aids-infection-the-beginning-of-the-end-for-today-s-greatest-pandemic
#13
F Gutiérrez
Recently, there have been significant advances in the fight against human immunodeficiency virus, which have increased the hopes of definitively halting its dissemination and of starting the decline of the epidemic it has caused. Transmission of the infection was drastically reduced when infected patients were given antiretroviral treatments, which boosted the diffusion of treatments to middle- and low-income countries. Global therapy coverage has doubled in recent years; meanwhile the incidence of new infections has decreased...
June 1, 2017: Revista Clínica Española
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#14
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28564629/comparison-between-roche-and-xpert-in-hiv-1-rna-quantitation-a-high-concordance-between-the-two-techniques-except-for-a-crf02_ag-subtype-variant-with-high-viral-load-titters-detected-by-roche-but-undetected-by-xpert
#15
Boaz Avidor, Natalia Matus, Shirley Girshengorn, Svetlana Achsanov, Simona Gielman, Irene Zeldis, Inbal Schweitzer, Amos Adler, Dan Turner
BACKGROUND: HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. OBJECTIVES: To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory...
May 19, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28558662/evaluation-of-gene-xpert-for-routine-diagnosis-of-hiv-associated-tuberculosis-in-nigeria-a-prospective-cohort-study
#16
Maxwell Oluwole Akanbi, Chad Achenbach, Babafemi Taiwo, John Idoko, Agatha Ani, Yetunde Isa, Oche Agbaji, Christiana Ukoli, Patrick Akande, Mamoudou Maiga, Robert Leo Murphy
BACKGROUND: Xpert MTB/Rif (Xpert) is described as a game changer in tuberculosis (TB) control. We evaluated the impact of Xpert on diagnosis, time to treatment, and treatment outcome among patients with HIV associated TB in Nigeria. METHODS: Adults with HIV being evaluated for pulmonary TB (PTB) were consecutively enrolled into the study cohort. At baseline, expectorated sputa were examined using Xpert and smear microscopy for Mycobacterium tuberculosis (MTB) and acid fast bacilli, respectively...
May 30, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28553929/silencing-of-hiv-1-by-agoshrna-molecules
#17
E Herrera-Carrillo, A Harwig, B Berkhout
RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by the expression of a short hairpin RNA (shRNA). shRNA molecules enter the RNAi pathway at the Dicer processing step. Recent studies indicated that the cellular microRNA (miRNA) miR-451 is not recognized by Dicer, but that is processed instead by the Argonaute 2 (Ago2) protein. Subsequently, Dicer-independent shRNAs were described that rely on Ago2 for processing as well as the subsequent silencing step. We called these AgoshRNA molecules because they depend on Ago2 both for maturation and activation...
May 29, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28553415/use-of-proviral-dna-to-investigate-virus-resistance-mutations-in-hiv-infected-zimbabweans
#18
Tutsirai V Musingwini, Danai T Zhou, Doreen Mhandire, Kerina Duri, Exnevia Gomo, Olav Oktedalen, Benjamin Chimukangara, Tinei Shamu, Sandra Shawarira-Bote, Collet Dandara, Babill Stray-Pedersen
BACKGROUND: Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations. OBJECTIVE: To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic. METHODS: DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software...
2017: Open Microbiology Journal
https://www.readbyqxmd.com/read/28550974/eliminating-hiv-1-packaging-sequences-from-lentiviral-vector-proviruses-enhances-safety-and-expedites-gene-transfer-for-gene-therapy
#19
Conrad A Vink, John R Counsell, Dany P Perocheau, Rajvinder Karda, Suzanne M K Buckley, Martijn H Brugman, Melanie Galla, Axel Schambach, Tristan R McKay, Simon N Waddington, Steven J Howe
Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#20
Elena Herrera-Carrillo, Ben Berkhout
Allogeneic transplantation of blood stem cells from a CCR5-Δ32 homozygous donor to an HIV-infected individual, the "Berlin patient", led to a cure. Since then there has been a search for approaches that mimic this intervention in a gene therapy setting. RNA interference (RNAi) has evolved as a powerful tool to regulate gene expression in a sequence-specific manner and can be used to inactivate the CCR5 mRNA. Short hairpin RNA (shRNA) molecules can impair CCR5 expression, but these molecules may cause unintended side effects and they will not be processed in cells that lack Dicer, such as monocytes...
2017: PloS One
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