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https://www.readbyqxmd.com/read/29221753/pura-the-gene-encoding-pur-alpha-member-of-an-ancient-nucleic-acid-binding-protein-family-with-mammalian-neurological-functions
#1
REVIEW
Dianne C Daniel, Edward M Johnson
The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1-4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements...
December 5, 2017: Gene
https://www.readbyqxmd.com/read/29220350/deep-sequencing-of-near-full-length-hiv-1-genomes-from-plasma-identifies-circulating-subtype-c-and-infrequent-occurrence-of-ac-recombinant-form-in-southern-india
#2
Shuba Varshini Alampalli, Michael M Thomson, Raghavan Sampathkumar, Karthi Sivaraman, Anto Jesuraj U K J, Chirag Dhar, George D Souza, Neil Berry, Annapurna Vyakarnam
India has the third largest number of HIV-1-infected individuals accounting for approximately 2.1 million people, with a predominance of circulating subtype C strains and a low prevalence of subtype A and A1C and BC recombinant forms, identified over the past two decades. Recovery of near full-length HIV-1 genomes from a plasma source coupled with advances in next generation sequencing (NGS) technologies and development of universal methods for amplifying whole genomes of HIV-1 circulating in a target geography or population provides the opportunity for a detailed analysis of HIV-1 strain identification, evolution and dynamics...
2017: PloS One
https://www.readbyqxmd.com/read/29215041/crispr-cas9-delivery-with-one-single-adenoviral-vector-devoid-of-all-viral-genes
#3
Eric Ehrke-Schulz, Maren Schiwon, Theo Leitner, Stephan Dávid, Thorsten Bergmann, Jing Liu, Anja Ehrhardt
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211501/viral-subversion-of-apobec3s-lessons-for-anti-tumor-immunity-and-tumor-immunotherapy
#4
Faezeh Borzooee, Mahdi Asgharpour, Emma Quinlan, Michael D Grant, Mani Larijani
APOBEC3s (A3) are endogenous DNA-editing enzymes that are expressed in immune cells including T lymphocytes. A3s target and mutate the genomes of retroviruses that infect immune tissues such as the human immunodeficiency virus (HIV). Therefore, A3s were classically defined as host anti-viral innate immune factors. In contrast, we and others showed that A3s can also benefit the virus by mediating escape from adaptive immune recognition and drugs. Crucially, whether A3-mediated mutations help or hinder HIV, is not up to chance...
December 6, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29209209/nonribosomal-peptides-from-marine-microbes-and-their-antimicrobial-and-anticancer-potential
#5
REVIEW
Shivankar Agrawal, Debabrata Acharya, Alok Adholeya, Colin J Barrow, Sunil K Deshmukh
Marine environments are largely unexplored and can be a source of new molecules for the treatment of many diseases such as malaria, cancer, tuberculosis, HIV etc. The Marine environment is one of the untapped bioresource of getting pharmacologically active nonribosomal peptides (NRPs). Bioprospecting of marine microbes have achieved many remarkable milestones in pharmaceutics. Till date, more than 50% of drugs which are in clinical use belong to the nonribosomal peptide or mixed polyketide-nonribosomal peptide families of natural products isolated from marine bacteria, cyanobacteria and fungi...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29208937/elucidating-the-in-vivo-interactome-of-hiv-1-rna-by-hybridization-capture-and-mass-spectrometry
#6
Rachel A Knoener, Jordan T Becker, Mark Scalf, Nathan M Sherer, Lloyd M Smith
HIV-1 replication requires myriad interactions between cellular proteins and the viral unspliced RNA. These interactions are important in archetypal RNA processes such as transcription and translation as well as for more specialized functions including alternative splicing and packaging of unspliced genomic RNA into virions. We present here a hybridization capture strategy for purification of unspliced full-length HIV RNA-protein complexes preserved in vivo by formaldehyde crosslinking, and coupled with mass spectrometry to identify HIV RNA-protein interactors in HIV-1 infected cells...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29206233/genome-wide-admixture-and-association-study-of-subclinical-atherosclerosis-in-the-women-s-interagency-hiv-study-wihs
#7
Aditi Shendre, Howard W Wiener, Marguerite R Irvin, Bradley E Aouizerat, Edgar T Overton, Jason Lazar, Chenglong Liu, Howard N Hodis, Nita A Limdi, Kathleen M Weber, Stephen J Gange, Degui Zhi, Michelle A Floris-Moore, Ighovwerha Ofotokun, Qibin Qi, David B Hanna, Robert C Kaplan, Sadeep Shrestha
Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis...
2017: PloS One
https://www.readbyqxmd.com/read/29203900/intracellular-immunization-against-hiv-infection-with-an-intracellular-antibody-that-mimics-hiv-integrase-binding-to-the-cellular-ledgf-protein
#8
Leyuan Bao, Clare Hannon, Abimael Cruz-Mignoni, Denis Ptchelkine, Mei-Yi Sun, Ami Miller, Wilawan Bunjobpol, Camilo E Quevedo, Mariliza Derveni, Jennifer Chambers, Alison Simmons, Simon E V Phillips, Terence H Rabbitts
Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29201613/genome-editing-for-cancer-therapy-delivery-of-cas9-protein-sgrna-plasmid-via-a-gold-nanocluster-lipid-core-shell-nanocarrier
#9
Peng Wang, Lingmin Zhang, Yangzhouyun Xie, Nuoxin Wang, Rongbing Tang, Wenfu Zheng, Xingyu Jiang
The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 (CRISPR-associated protein) system (CRISPR-Cas9) is a powerful toolbox for gene-editing, however, the nonviral delivery of CRISPR-Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV-1-transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei...
November 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29194114/hiv-1-and-hepatitis-c-virus-selection-bottleneck-in-chinese-people-who-inject-drugs
#10
Fan Li, Liying Ma, Yi Feng, Yuhua Ruan, Jing Hu, Hongshuo Song, Pengtao Liu, Jun Ma, Baolin Rui, Kate Kerpen, Benjamin Scheinfeld, Tuhina Srivastava, Metzger David, Hui Li, Katharine J Bar, Yiming Shao
OBJECTIVES: For both HIV-1 and hepatitis C virus (HCV), assessing the stringency of the transmission process is a scientific priority. Enumerations of transmitted/founder (TF) viruses have shown a strict transmission bottleneck in sexual transmission of HIV-1 and a wide range in the multiplicity of infection in HCV. Here, we aim to determine the stringency of parenteral transmission for HIV -1 and HCV in people who inject drugs (PWID). DESIGN: We used molecular sequencing and several complementary analyses to enumerate the TF HIV-1 and HCV variants in a well-described cohort of PWID in Xinjiang, China...
November 30, 2017: AIDS
https://www.readbyqxmd.com/read/29187544/genetically-intact-but-functionally-impaired-hiv-1-env-glycoproteins-in-the-t-cell-reservoir
#11
Anne de Verneuil, Julie Migraine, Fabrizio Mammano, Jean-Michel Molina, Sébastien Gallien, Hugo Mouquet, Allan J Hance, François Clavel, Jacques Dutrieux
HIV-infected subjects under ART harbor a persistent viral reservoir in resting CD4+ T-cells, which accounts for the resurgence of HIV replication after ART interruption. A large majority of HIV reservoir genomes are genetically defective, but even among intact proviruses, few seem able to generate infectious virus. To understand this phenomenon, we have examined the function and expression of HIV envelope glycoproteins reactivated from the reservoir of 4 HIV-infected subjects under suppressive ART. We studied full-length genetically intact env sequences from both replicative viruses and cell-associated mRNAs...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29187540/a-general-model-for-retroviral-capsid-pattern-recognition-by-trim5-proteins
#12
Jonathan M Wagner, Devin E Christensen, Akash Bhattacharya, Daria M Dawidziak, Marcin D Roganowicz, Yueping Wan, Ruth A Pumroy, Borries Demeler, Dmitri N Ivanov, Barbie K Ganser-Pornillos, Wesley I Sundquist, Owen Pornillos
Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity (KD >1 mM), and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher (KD ∼10 μM) affinity for isolated capsid subunits...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186559/phyloscanner-inferring-transmission-from-within-and-between-host-pathogen-genetic-diversity
#13
Chris Wymant, Matthew Hall, Oliver Ratmann, David Bonsall, Tanya Golubchik, Mariateresa de Cesare, Astrid Gall, Marion Cornelissen, Christophe Fraser
A central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone...
November 23, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29181236/machine-learning-to-improve-the-effectiveness-of-anrs-in-predicting-hiv-drug-resistance
#14
Yashik Singh
Objectives: Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is one of the major burdens of disease in developing countries, and the standard-of-care treatment includes prescribing antiretroviral drugs. However, antiretroviral drug resistance is inevitable due to selective pressure associated with the high mutation rate of HIV. Determining antiretroviral resistance can be done by phenotypic laboratory tests or by computer-based interpretation algorithms...
October 2017: Healthcare Informatics Research
https://www.readbyqxmd.com/read/29180782/alpha-helicoidal-heat-like-repeat-proteins-%C3%AE-rep-selected-as-interactors-of-hiv-1-nucleocapsid-negatively-interfere-with-viral-genome-packaging-and-virus-maturation
#15
Sudarat Hadpech, Sawitree Nangola, Koollawat Chupradit, Kanda Fanhchaksai, Wilhelm Furnon, Agathe Urvoas, Marie Valerio-Lepiniec, Philippe Minard, Pierre Boulanger, Saw-See Hong, Chatchai Tayapiwatana
A new generation of artificial proteins, derived from alpha-helicoidal HEAT-like repeat protein scaffolds (αRep), was previously characterized as an effective source of intracellular interfering proteins. In this work, a phage-displayed library of αRep was screened on a region of HIV-1 Gag polyprotein encompassing the C-terminal domain of the capsid, the SP1 linker and the nucleocapsid. This region is known to be essential for the late steps of HIV-1 life cycle, Gag oligomerization, viral genome packaging and the last cleavage step of Gag, leading to mature, infectious virions...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180435/bicaudal-d2-facilitates-the-cytoplasmic-trafficking-and-nuclear-import-of-hiv-1-genomes-during-infection
#16
Adarsh Dharan, Silvana Opp, Omar Abdel-Rahim, Sevnur Komurlu Keceli, Sabrina Imam, Felipe Diaz-Griffero, Edward M Campbell
Numerous viruses, including HIV-1, exploit the microtubule network to traffic toward the nucleus during infection. Although numerous studies have observed a role for the minus-end microtubule motor dynein in HIV-1 infection, the mechanism by which the viral core containing the viral genome associates with dynein and induces its perinuclear trafficking has remained unclear. Here, we report that the dynein adapter protein bicaudal D2 (BICD2) is able to interact with HIV-1 viral cores in target cells. We also observe that BICD2 can bind in vitro-assembled capsid tubes through its CC3 domain...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29179726/modulation-of-the-functional-association-between-the-hiv-1-intasome-and-the-nucleosome-by-histone-amino-terminal-tails
#17
Mohamed S Benleulmi, Julien Matysiak, Xavier Robert, Csaba Miskey, Eric Mauro, Delphine Lapaillerie, Paul Lesbats, Stéphane Chaignepain, Daniel R Henriquez, Christina Calmels, Oyindamola Oladosu, Eloïse Thierry, Oscar Leon, Marc Lavigne, Marie-Line Andreola, Olivier Delelis, Zoltán Ivics, Marc Ruff, Patrice Gouet, Vincent Parissi
BACKGROUND: Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process...
November 28, 2017: Retrovirology
https://www.readbyqxmd.com/read/29169687/understanding-the-inhibitory-mechanism-of-bit225-drug-against-p7-viroporin-using-computational-study
#18
Esmaeil Behmard, Parviz Abdolmaleki, Majid Taghdir
P7 is the only viral channel encoded by the Hepatitis C Virus (HCV) genome. It is a small, highly hydrophobic protein containing 63 amino acids. Structural studies have shown that p7 has two transmembrane (TM) α helices linked by a short dibasic cytoplasmic loop. P7, mostly placed in the endoplasmic reticulum (ER), is a membrane-associated protein. The results obtained from different studies revealed that p7 is a polytopic membrane protein that could oligomerize in membrane bilayer to create ion channels with cation selectivity...
November 16, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29163915/field-deployable-quantitative-rapid-identification-of-active-ebola-virus-infection-in-unprocessed-blood
#19
Kavit Shah, Emma Bentley, Adam Tyler, Kevin S R Richards, Edward Wright, Linda Easterbrook, Diane Lee, Claire Cleaver, Louise Usher, Jane E Burton, James K Pitman, Christine B Bruce, David Edge, Martin Lee, Nelson Nazareth, David A Norwood, Sterghios A Moschos
The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29162040/cloning-and-expression-of-bpmyc4-and-bpbhlh9-genes-and-the-role-of-bpbhlh9-in-triterpenoid-synthesis-in-birch
#20
Jing Yin, Xin Li, Yaguang Zhan, Ying Li, Ziyue Qu, Lu Sun, Siyao Wang, Jie Yang, Jialei Xiao
BACKGROUND: Birch (Betula platyphylla Suk.) contains triterpenoids with anti-HIV and anti-tumor pharmacological activities. However, the natural abundance of these triterpenoids is low, and their chemical synthesis is costly. Transcription factors have the ability to regulate the metabolite pathways of triterpenoids via multi-gene control, thereby improving metabolite yield. Thus, transcription factors have the potential to facilitate the production of birch triterpenoids. Plant bHLH (basic helix-loop-helix) transcription factors play important roles in stress response and secondary metabolism...
November 21, 2017: BMC Plant Biology
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