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HIV sequence

Almudena Cascajero, Alberto Rastrojo, Francisco Díez-Fuertes, Beatriz Hernández-Novoa, Begoña Aguado, Santiago Moreno, José Alcami, Mayte Pérez-Olmeda
In this study we have characterized quasispecies dynamics and the evolution of viral tropism in naive HIV-1-infected patients treated with a short-course of maraviroc monotherapy (NCT01060618) independently of their tropism. We randomly selected 20 patients displaying different basal tropism -10 R5 and 10 DMX4- at recruitment as determined by phenotypic tests (Trofile® ). Evolution of viral quasiespecies at the end of treatment was determined by ultra-deep sequencing of the V3 region using a 454 Life Sciences Platform and geno2pheno (g2p) algorithm for viral tropism prediction...
March 21, 2018: Journal of Virology
Yongao Xiong, Qiongyu Li, Muchena J Kailemia, Carlito B Lebrilla, Somen Nandi, Karen A McDonald
Kifunensine, a potent and selective inhibitor of class I α-mannosidases, prevents α-mannosidases I from trimming mannose residues on glycoproteins, thus resulting in oligomannose-type glycans. We report for the first time that through one-time vacuum infiltration of kifunensine in plant tissue, N-linked glycosylation of a recombinant protein transiently produced in whole-plants shifted completely from complex-type to oligomannose-type. Fc-fused capillary morphogenesis protein 2 (CMG2-Fc) containing one N -glycosylation site on the Fc domain, produced in Nicotiana benthamiana whole plants, served as a model protein...
March 17, 2018: International Journal of Molecular Sciences
Benson R Kidenya, Stephen E Mshana, Daniel W Fitzgerald, Oksana Ocheretina
BACKGROUND: Drug resistant Tuberculosis (TB) is considered a global public health threat. Whole-genome sequencing (WGS) is a new technology for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles and genotypes for epidemiologic surveillance. Therefore, we used WGS to determine genotypic drug resistance profiles and genetic diversity of drug resistant Mycobacterium tuberculosis isolates from Mwanza, North-western Tanzania. METHODS: A cross-sectional study was conducted at the Bugando Medical Center (BMC) from September 2014 to June 2015...
March 2018: Tuberculosis
Seong-Hyun Park, Kyung-Lee Yu, Yu-Mi Jung, Seong-Deok Lee, Ji Chang You
Transcription termination factor-1 (TTF-I) is an RNA polymerase 1-mediated transcription terminator and consisting of a C-terminal DNA-binding domain, central domain, and N-terminal regulatory domain. This protein binds to a so-called 'Sal box' composed of an 11-base pair motif. The interaction of TTF-I with the 'Sal box' is important for many cellular events, including efficient termination of RNA polymerase-1 activity involved in pre-rRNA synthesis and formation of a chromatin loop. To further understand the role of TTF-I in human immunodeficiency virus (HIV)-I virus production, we generated various TTF-I mutant forms...
March 20, 2018: BMB Reports
Hannah F Löchel, Mona Riemenschneider, Dmitrij Frishman, Dominik Heider
Motivation: The V3 loop of the gp120 glycoprotein of the Human Immunodeficiency Virus 1 (HIV-1) is considered to be responsible for viral coreceptor tropism. gp120 interacts with the CD4 receptor of the host cell and subsequently V3 binds either CCR5 or CXCR4. Due to the fact that the CCR5 coreceptor is targeted by entry inhibitors, a reliable prediction of the coreceptor usage of HIV-1 is of great interest for antiretroviral therapy. Although several methods for the prediction of coreceptor tropism are available, almost all of them have been developed based on only subtype B sequences, and it has been shown in several studies that the prediction of non-B sequences, in particular subtype A sequences, are less reliable...
March 15, 2018: Bioinformatics
Kombo F N'Guessan, Ceejay Boyce, Awewura Kwara, Timothy N A Archampong, Margaret Lartey, Kwamena W Sagoe, Ernest Kenu, Adjoa Obo-Akwa, Jason T Blackard
Human pegivirus (HPgV) is a positive single-stranded RNA virus in the Flaviviridae family. Phylogenetic analysis reveals the presence of multiple HPgV genotypes with distinct geographic locations. HPgV is of interest because of its potential beneficial impact on HIV disease progression. Despite this, the effects of HPgV in the context of other viral infections, such as hepatitis B virus (HBV), are poorly understood, and data from resource-limited settings are scarce. Therefore, we conducted a cross-sectional analysis of HPgV in HIV/HBV co-infected patients in Ghana...
March 17, 2018: Virus Genes
Ulrike C Lange, Julia K Bialek, Thomas Walther, Joachim Hauber
HIV infection is characterized by accumulation of proviral sequences within the human host genome. Integration of viral-derived DNA occurs at preferential loci, suggesting a site-specific crosstalk between viral sequences and human genes. We here describe a genome engineering workflow to generate models for HIV-1 infection that for the first time recapitulate proviral integration at selected genomic loci and provide unique tools to study effects of HIV proviral integration site choice. Using this workflow, we have derived two BACH2-HIV-1 reporter models that mimic largely latent integration in the clinically relevant BACH2 gene locus, which has been associated with recurrent integration and HIV-reservoir maintenance in chronically infected patients...
March 14, 2018: Virus Research
Dominik Brado, Adetayo Emmanuel Obasa, George Mondinde Ikomey, Ruben Cloete, Kamalendra Singh, Susan Engelbrecht, Ujjwal Neogi, Graeme Brendon Jacobs
HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2...
March 16, 2018: Scientific Reports
Annesa Flentje, Kord Kober, Adam Carrico, Torsten B Neilands, Elena Flowers, Nicholas Heck, Bradley Aouizerat
Sexual minority (i.e., non-heterosexual) individuals experience poorer mental and physical health, accounted for in part by the additional burden of sexual minority stress occurring from being situated in a culture favoring heteronormativity. Informed by previous research, the purpose of this study was to identify the relationship between sexual minority stress and leukocyte gene expression related to inflammation, cancer, immune function, and cardiovascular function. Sexual minority men living with HIV who were on anti-retroviral medication, had viral load <200 copies/mL, and had biologically confirmed, recent methamphetamine use completed minority stress measures and submitted blood samples for RNA sequencing on leukocytes...
March 13, 2018: Brain, Behavior, and Immunity
Tongqing Zhou, Anqi Zheng, Ulrich Baxa, Gwo-Yu Chuang, Ivelin S Georgiev, Rui Kong, Sijy O'Dell, Syed Shahzad-Ul-Hussan, Chen-Hsiang Shen, Yaroslav Tsybovsky, Robert T Bailer, Syna K Gift, Mark K Louder, Krisha McKee, Reda Rawi, Catherine H Stevenson, Guillaume B E Stewart-Jones, Justin D Taft, Eric Waltari, Yongping Yang, Baoshan Zhang, Sachin S Shivatare, Vidya S Shivatare, Chang-Chun D Lee, Chung-Yi Wu, James C Mullikin, Carole A Bewley, Dennis R Burton, Victoria R Polonis, Lawrence Shapiro, Chi-Huey Wong, John R Mascola, Peter D Kwong, Xueling Wu
Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the "silent face" on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center...
March 7, 2018: Immunity
Manon Ragonnet-Cronin, Celia Jackson, Amanda Bradley-Stewart, Celia Aitken, Andrew McAuley, Norah Palmateer, Rory Gunson, David Goldberg, Catriona Milosevic, Andrew J Leigh Brown
Harm reduction has dramatically reduced HIV incidence among people who inject drugs (PWID). In Glasgow, Scotland, <10 infections/year have been diagnosed among PWID since the mid-90s. However, in 2015 a sharp rise in diagnoses was noted among PWID: many were subtype C with two identical drug resistant mutations and some displayed low avidity, suggesting the infections were linked and recent.We collected Scottish pol sequences and identified closely related sequences from public databases. Genetic linkage was ascertained among 228 Scottish, 1820 UK and 524 global sequences...
March 13, 2018: Journal of Infectious Diseases
Seung Yub Han, Alesia Antoine, David Howard, Bryant Chang, Woo Sung Chang, Matthew Slein, Gintaras Deikus, Sofia Kossida, Patrice Duroux, Marie-Paule Lefranc, Robert P Sebra, Melissa L Smith, Ismael Ben F Fofana
The simian immunodeficiency virus (SIV)/macaque model of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome pathogenesis is critical for furthering our understanding of the role of antibody responses in the prevention of HIV infection, and will only increase in importance as macaque immunoglobulin (IG) gene databases are expanded. We have previously reported the construction of a phage display library from a SIV-infected rhesus macaque ( Macaca mulatta ) using oligonucleotide primers based on human IG gene sequences...
2018: Frontiers in Immunology
F Nici, G Oliviero, A P Falanga, S D'Errico, M Marzano, D Musumeci, D Montesarchio, S Noppen, C Pannecouque, G Piccialli, N Borbone
By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5'CGGA3' to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1-3) having the sequence 5'CGGAGG3' were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5' position, the 5' ends of 1-3 were left uncapped (1) or capped with either the lipophilic dimethoxytrityl (DMT) (2) or the hydrophilic glucosyl-4-phosphate (3) moieties...
March 15, 2018: Organic & Biomolecular Chemistry
Homero San-Juan-Vergara, Eduardo Zurek, Nadim J Ajami, Christian Mogollon, Mario Peña, Ivan Portnoy, Jorge I Vélez, Christian Cadena-Cruz, Yirys Diaz-Olmos, Leidy Hurtado-Gómez, Silvana Sanchez-Sit, Danitza Hernández, Irina Urruchurtu, Pierina Di-Ruggiero, Ella Guardo-García, Nury Torres, Oscar Vidal-Orjuela, Diego Viasus, Joseph F Petrosino, Guillermo Cervantes-Acosta
HIV infection has a tremendous impact on the immune system's proper functioning. The mucosa-associated lymphoid tissue (MALT) is significantly disarrayed during HIV infection. Compositional changes in the gut microbiota might contribute to the mucosal barrier disruption, and consequently to microbial translocation. We performed an observational, cross-sectional study aimed at evaluating changes in the fecal microbiota of HIV-infected individuals from Colombia. We analyzed the fecal microbiota of 37 individuals via 16S rRNA gene sequencing; 25 HIV-infected patients and 12 control (non-infected) individuals, which were similar in body mass index, age, gender balance and socioeconomic status...
March 14, 2018: Scientific Reports
J von Felden, J Vermehren, P Ingiliz, S Mauss, T Lutz, K G Simon, H W Busch, A Baumgarten, K Schewe, D Hueppe, C Boesecke, J K Rockstroh, M Daeumer, N Luebke, J Timm, J Schulze Zur Wiesch, C Sarrazin, S Christensen
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting...
March 14, 2018: Alimentary Pharmacology & Therapeutics
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Stefan Gahbauer, Kristyna Pluhackova, Rainer A Böckmann
Chemokine receptors, a subclass of G protein coupled receptors (GPCRs), play essential roles in the human immune system, they are involved in cancer metastasis as well as in HIV-infection. A plethora of studies show that homo- and heterodimers or even higher order oligomers of the chemokine receptors CXCR4, CCR5, and CCR2 modulate receptor function. In addition, membrane cholesterol affects chemokine receptor activity. However, structural information about homo- and heterodimers formed by chemokine receptors and their interplay with cholesterol is limited...
March 12, 2018: PLoS Computational Biology
Alphonse Garcia
Small viral proteins with cationic domains can be involved in multiple biological processes including cell penetration or interaction with intracellular targets. Within the last two decades several reports indicated that the C-terminus of HIV-1 Vpr is a cell penetrating sequence, a PP2A-dependent death domain and also displays toxicity against Gram-negative E. coli. Interestingly, HIV-1 Vpr, as well as some cationic proteins encoded by different viruses, share similar physical properties with the unique anti-microbial human cathelicidin LL37 peptide...
April 2018: Medical Hypotheses
Enkelejda Miho, Alexander Yermanos, Cédric R Weber, Christoph T Berger, Sai T Reddy, Victor Greiff
The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires, thereby revealing the high-dimensional complexity of the immune receptor sequence landscape...
2018: Frontiers in Immunology
Redmond P Smyth, Maureen R Smith, Anne-Caroline Jousset, Laurence Despons, Géraldine Laumond, Thomas Decoville, Pierre Cattenoz, Christiane Moog, Fabrice Jossinet, Marylène Mougel, Jean-Christophe Paillart, Max von Kleist, Roland Marquet
Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell MIME) as a way to define RNA regulatory landscapes at single nucleotide resolution under native conditions. In cell MIME is based on (i) random mutation of an RNA target, (ii) expression of mutated RNA in cells, (iii) physical separation of RNA into functional and non-functional populations, and (iv) high-throughput sequencing to identify mutations affecting function...
March 5, 2018: Nucleic Acids Research
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