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https://www.readbyqxmd.com/read/27914932/detection-of-human-immunodeficiency-virus-rnas-in-living-cells-using-spinach-rna-aptamers
#1
Brandon D Burch, Carolina Garrido, David M Margolis
Many techniques currently used to measure HIV RNA production in cells suffer from limitations that include high background signal or the potential to destroy cellular context. Fluorophore-binding RNA aptamers offer the potential for visualizing RNAs directly in living cells with minimal cellular perturbation. We inserted a sequence encoding a fluorophore-binding RNA aptamer, known as Spinach, into the HIV genome such that predicted RNA secondary structures in both Spinach and HIV were preserved. Chimeric HIV-Spinach RNAs were functionally validated in vitro by testing their ability to enhance the fluorescence of a conditional fluorophore (DFHBI), which specifically binds Spinach...
November 30, 2016: Virus Research
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#2
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909304/transmission-of-multiple-hiv-1-subtype-c-transmitted-founder-viruses-into-the-same-recipients-was-not-determined-by-modest-phenotypic-differences
#3
Hongshuo Song, Bhavna Hora, Elena E Giorgi, Amit Kumar, Fangping Cai, Tanmoy Bhattacharya, Alan S Perelson, Feng Gao
A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#4
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27903602/whole-genome-sequencing-of-mycobacterium-tuberculosis-provides-insight-into-the-evolution-and-genetic-composition-of-drug-resistant-tuberculosis-in-belarus
#5
Kurt R Wollenberg, Christopher A Desjardins, Aksana Zalutskaya, Vervara Slodovnikova, Andrew J Oler, Mariam Quiñones, Thomas Abeel, Sinead B Chapman, Michael Tartakovsky, Andrei Gabrielian, Sven Hoffner, Aliaksandr Skrahin, Bruce W Birren, Alexander Rosenthal, Alena Skrahina, Ashlee M Earl
The emergence and spread of drug resistant Mycobacterium tuberculosis (DR-TB) is a critical global health issue. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138 M. tuberculosis isolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB...
November 30, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27900346/preclinical-development-and-qualification-of-zfn-mediated-ccr5-disruption-in-human-hematopoietic-stem-progenitor-cells
#6
David L DiGiusto, Paula M Cannon, Michael C Holmes, Lijing Li, Anitha Rao, Jianbin Wang, Gary Lee, Philip D Gregory, Kenneth A Kim, Samuel B Hayward, Kathleen Meyer, Colin Exline, Evan Lopez, Jill Henley, Nancy Gonzalez, Victoria Bedell, Rodica Stan, John A Zaia
Gene therapy for HIV-1 infection is a promising alternative to lifelong combination antiviral drug treatment. Chemokine receptor 5 (CCR5) is the coreceptor required for R5-tropic HIV-1 infection of human cells. Deletion of CCR5 renders cells resistant to R5-tropic HIV-1 infection, and the potential for cure has been shown through allogeneic stem cell transplantation with naturally occurring homozygous deletion of CCR5 in donor hematopoietic stem/progenitor cells (HSPC). The requirement for HLA-matched HSPC bearing homozygous CCR5 deletions prohibits widespread application of this approach...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27898590/reactivation-of-simian-immunodeficiency-virus-reservoirs-in-the-brain-of-virally-suppressed-macaques
#7
Lucio Gama, Celina M Abreu, Erin N Shirk, Sarah L Price, Ming Li, Greg M Laird, Kelly A Metcalf Pate, Stephen W Wietgrefe, Shelby L O'Connor, Luiz Pianowski, Ashley T Haase, Carine Van Lint, Robert F Siliciano, Janice E Clements
OBJECTIVE: Resting CD4 T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. DESIGN: Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious central nervous system-penetrant ART...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#8
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27893822/deciphering-multiplicity-of-hiv-1c-infection-transmission-of-closely-related-multiple-viral-lineages
#9
Vlad Novitsky, Sikhulile Moyo, Rui Wang, Simani Gaseitsiwe, M Essex
BACKGROUND: A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. METHODOLOGY: We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources...
2016: PloS One
https://www.readbyqxmd.com/read/27890949/p16-immunostaining-as-a-predictor-of-anal-and-cervical-dysplasia-in-women-attending-a-sexually-transmitted-infection-clinic
#10
Deepika Pandhi, Kavita Bisherwal, Archana Singal, Kiran Guleria, Kiran Mishra
BACKGROUND: Carcinogenesis caused by human papillomavirus (HPV) leads to over-expression of p16 protein. p16 may act as a marker of HPV integration with host genome and serve as a surrogate marker of HPV oncogenesis. MATERIALS AND METHODS: A single center study of 75 women (35 HIV-positive and 40 HIV-negative women) was conducted. Anal and cervical specimens were obtained for cytology and p16 immunostaining. RESULTS: The sensitivity of p16 to diagnose anal and cervical dysplasia was 50% and 58...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27888407/targeting-the-rhesus-macaque-trim5%C3%AE-gene-to-enhance-the-susceptibility-of-cd4-t-cells-to-hiv-1-infection
#11
Xiaoli Wang, Qing Yu, Yahong Yuan, Zhiping Teng, Dongsheng Li, Yi Zeng
The host range of human immunodeficiency virus type 1 (HIV-1) is extremely narrow, which has hampered the establishment of non-human primate models for HIV-1 infection. The species-specific innate immune factor tripartite motif 5 alpha (TRIM5α) is a key molecule that confers potent resistance against HIV-1 infection. In this study, we targeted the TRIM5α gene of rhesus macaques (rhTRIM5α) using the transcription activator-like effector nuclease (TALEN) to study the effect on HIV-1 infection. CD4(+) T cells were separated from the peripheral blood of rhesus macaques by magnetic cell sorting, and the positive rate was greater than 99%...
November 25, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#12
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27887868/reassessing-apobec3g-inhibition-by-hiv-1-vif-derived-peptides
#13
Christopher M Richards, Ming Li, Angela L Perkins, Anurag Rathore, Daniel A Harki, Reuben S Harris
The human APOBEC3G (A3G) enzyme restricts HIV-1 in the absence of the viral accessory protein viral infectivity factor (Vif) by deaminating viral cDNA cytosines to uracils. These uracil lesions base-pair with adenines during the completion of reverse transcription and result in A3G signature G-to-A mutations in the viral genome. Vif protects HIV-1 from A3G-mediated restriction by forming an E3-ubiquitin ligase complex to polyubiquitinate A3G and trigger its degradation. Prior studies indicated that Vif may also directly block the enzymatic activity of A3G and, provocatively, that Vif-derived peptides, Vif 25-39 and Vif 105-119, are similarly inhibitory...
November 22, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27886048/interactions-between-the-hiv-1-unspliced-mrna-and-host-mrna-decay-machineries
#14
REVIEW
Daniela Toro-Ascuy, Bárbara Rojas-Araya, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation...
November 23, 2016: Viruses
https://www.readbyqxmd.com/read/27882070/serological-patterns-and-molecular-characterization-of-occult-hepatitis-b-virus-infection-among-blood-donors
#15
Hong Lin, Hong Zhao, Xinyi Tang, Wenjia Hu, Nizheng Jiang, Shaowen Zhu, Chengyin Huang
BACKGROUND: Hepatitis B infections, characterized by the presence of a viral genome without detectable hepatitis B surface antigen (HBsAg; Occult hepatitis B infection [OBI]), have been reported recently. OBJECTIVES: We performed serological and molecular characterization of OBI among blood donors at Jiangsu province blood center during years 2013 and 2014. METHODS: All donor samples were routinely screened by double enzyme-linked immunosorbent assay (ELISA) for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), Treponema pallidum (TP), and alanine aminotransferase (ALT)...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27878300/induction-of-dna-damage-and-apoptosis-in-human-leukemia-cells-by-efavirenz
#16
Ansgar Brüning, Julia Jückstock, Bernd Kost, Panagiotis Tsikouras, Tobias Weissenbacher, Sven Mahner, Ioannis Mylonas
As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27875905/identification-of-novel-resistance-related-polymorphisms-in-hiv-1-subtype-c-rt-connection-and-rnase-h-domains-from-patients-under-virological-failure-in-brazil
#17
Maria Fernanda M Barral, Arielly K P Sousa, André F Santos, Celina M Abreu, Amilcar Tanuri, Marcelo A Soares
Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by PCR, DNA sequencing and phylogenetic analysis...
November 22, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27870832/position-effects-influence-hiv-latency-reversal
#18
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans, Guillaume J Filion
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27867372/overlapping-regions-in-hiv-1-genome-act-as-potential-sites-for-host-virus-interaction
#19
Deeya Saha, Soumita Podder, Tapash C Ghosh
More than a decade, overlapping genes in RNA viruses became a subject of research which has explored various effect of gene overlapping on the evolution and function of viral genomes like genome size compaction. Additionally, overlapping regions (OVRs) are also reported to encode elevated degree of protein intrinsic disorder (PID) in unspliced RNA viruses. With the aim to explore the roles of OVRs in HIV-1 pathogenesis, we have carried out an in-depth analysis on the association of gene overlapping with PID in 35 HIV1- M subtypes...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27865749/in-vitro-functional-assessment-of-natural-hiv-1-group-m-vpu-sequences-using-a-universal-priming-approach
#20
Asa Rahimi, Gursev Anmole, Maribel Soto-Nava, Tania Escamilla-Gomez, Tristan Markle, Steven W Jin, Guinevere Q Lee, P Richard Harrigan, David R Bangsberg, Jeffrey Martin, Santiago Avila-Rios, Gustavo Reyes-Teran, Mark A Brockman, Zabrina L Brumme
The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype)...
November 16, 2016: Journal of Virological Methods
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