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https://www.readbyqxmd.com/read/28100831/coexistence-of-potent-hiv-1-broadly-neutralizing-antibodies-and-antibody-sensitive-viruses-in-a-viremic-controller
#1
Natalia T Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A Sievers, Devin Sok, Hui Cai, Julio C Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B Gristick, Marit J van Gils, Rogier W Sanders, Lai-Xi Wang, Michael S Seaman, Dennis R Burton, Anna Gazumyan, Bruce D Walker, Anthony P West, Pamela J Bjorkman, Michel C Nussenzweig
Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env)...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28099825/transmission-of-extensively-drug-resistant-tuberculosis-in-south-africa
#2
N Sarita Shah, Sara C Auld, James C M Brust, Barun Mathema, Nazir Ismail, Pravi Moodley, Koleka Mlisana, Salim Allana, Angela Campbell, Thuli Mthiyane, Natashia Morris, Primrose Mpangase, Hermina van der Meulen, Shaheed V Omar, Tyler S Brown, Apurva Narechania, Elena Shaskina, Thandi Kapwata, Barry Kreiswirth, Neel R Gandhi
Background Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. Methods We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014...
19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28099408/multiphenotype-association-study-of-patients-randomized-to-initiate-antiretroviral-regimens-in-aids-clinical-trials-group-protocol-a5202
#3
Anurag Verma, Yuki Bradford, Shefali S Verma, Sarah A Pendergrass, Eric S Daar, Charles Venuto, Gene D Morse, Marylyn D Ritchie, David W Haas
BACKGROUND: High-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202. PARTICIPANTS AND METHODS: From among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog...
January 5, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28096489/induced-packaging-of-cellular-micrornas-into-hiv-1-virions-can-inhibit-infectivity
#4
Hal P Bogerd, Edward M Kennedy, Adam W Whisnant, Bryan R Cullen
: Analysis of the incorporation of cellular microRNAs (miRNAs) into highly purified HIV-1 virions revealed that this largely, but not entirely, mirrored the level of miRNA expression in the producer CD4(+) T cells. Specifically, of the 58 cellular miRNAs detected at significant levels in the producer cells, only 5 were found in virions at a level 2- to 4-fold higher than that predicted on the basis of random cytoplasmic sampling. Of note, these included two miRNAs, miR-155 and miR-92a, that were reported previously to at least weakly bind HIV-1 transcripts...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28088235/the-sense-behind-retroviral-anti-sense-transcription
#5
Mamneet Manghera, Alycia Magnusson, Renée N Douville
Retroviruses are known to rely extensively on the expression of viral proteins from the sense proviral genomic strand. Yet, the production of regulatory retroviral proteins from antisense-encoded viral genes is gaining research attention, due to their clinical significance. This report will discuss what is known about antisense transcription in Retroviridae, and provide new information about antisense transcriptional regulation through a comparison of Human Immunodeficiency Virus (HIV), Human T-cell Lymphotrophic Virus (HTLV-1) and endogenous retrovirus-K (ERVK) long terminal repeats (LTRs)...
January 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#6
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28086981/does-antiretroviral-treatment-change-hiv-1-codon-usage-patterns-in-its-genes-a-preliminary-bioinformatics-study
#7
Navaneethan Palanisamy, Nathan Osman, Frédéric Ohnona, Hong-Tao Xu, Bluma Brenner, Thibault Mesplède, Mark A Wainberg
BACKGROUND: Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias...
January 7, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28077653/characterizing-hiv-1-splicing-using-next-generation-sequencing
#8
Ann Emery, Shuntai Zhou, Elizabeth Pollom, Ronald Swanstrom
: Full-length HIV-1 RNA serves as the genome or as an mRNA, or this RNA undergoes splicing using four donors and ten acceptors to create over 50 physiologically relevant transcripts in two size classes (1.8 kb and 4 kb). We developed an assay using Primer ID-tagged deep sequencing to quantify HIV-1 splicing. Using the NL4-3 lab strain we found that A5 (env/nef) is the most commonly used acceptor (about 50%) with A3 (tat) the least used (about 3%). Two small exons are made when a splice to acceptor A1 or A2 is followed by activation of donor D2 or D3, and the high-level use of D2 and D3 dramatically reduces the amount of vif and vpr transcripts...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077647/sensitive-next-generation-sequencing-method-reveals-deep-genetic-diversity-of-hiv-1-in-the-democratic-republic-of-the-congo
#9
M A Rodgers, E Wilkerson, A Vallari, C McArthur, L Sthreshley, C A Brennan, G Cloherty, T de Oliveira
: As the epidemiological epicentre of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077634/characterization-of-hcv-envelope-diversification-from-acute-to-chronic-infection-using-smrt-sequencing-within-a-sexually-transmitted-hepatitis-c-virus-cluster
#10
Cynthia K Y Ho, Jayna Raghwani, Sylvie Koekkoek, Richard H Liang, Jan T M Van der Meer, Marc Van Der Valk, Menno De Jong, Oliver G Pybus, Janke Schinkel, Richard Molenkamp
: In contrast to other available next generation sequencing platforms, Pacbio Single Molecule, Real-Time (SMRT) sequencing has the advantage of generating long reads, albeit with a relatively higher error rate in unprocessed data. Using this platform we longitudinally sampled and sequenced the hepatitis C virus (HCV) envelope genome region (1680 nt) from individuals belonging to a cluster of sexually-transmitted cases. All five subjects were HIV-1 coinfected and infected with a closely related strain of HCV genotype 4d...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077632/phyloepidemiological-analysis-reveals-that-viral-divergence-led-to-the-paucity-of-sivmus-gsn-mon-infections-in-wild-populations
#11
Fabian Schmidt, Florian Liegeois, Edward J D Greenwood, Matthew LeBreton, James Lester, Luc Deleplancque, Martine Peeters, Avelin Aghokeng, Ubald Tamoufe, Joseph L D Diffo, Jean M Takuo, Nathan D Wolfe, Eric Leroy, François Rouet, Jonathan L Heeney
: Human immunodeficiency virus subtype-1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalence and uneven geographical distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn respectively, have also low rates of SIV infections in their populations...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28075146/five-near-full-length-hepatitis-c-virus-sequences-were-isolated-from-hiv-coinfected-idus-of-china
#12
Fan Li, Yi Feng, Na Ni, Jing Hu, Yuhua Ruan, Yiming Shao, Liying Ma
HIV and HCV share transmission routes including contaminated blood transfusion, sexual intercourse, and needle-sharing in injection drug users (IDUs). We obtained five near full-length genome sequences (NFLGs) of HCV isolated from five HIV-1 coinfected IDUs in Sichuan and Xinjiang province, China. By conducting reconstruction of neighbor-joining (NJ) phylogenetic tree, our results revealed that the five isolates are different genotypes (1b, 3a, 6a and 6n). The amino acid substitutions(170I) in XJN0021 related to resistant to protease inhibitors (Grazoprevir) were also identified...
January 11, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28073289/generation-and-characterization-of-hiv-1-transmitted-and-founder-virus-consensus-sequence-from-intravenous-drug-users-in-xinjiang-china
#13
Fan Li, Liying Ma, Yi Feng, Jing Hu, Na Ni, Yuhua Ruan, Yiming Shao
HIV-1 transmission in intravenous drug users (IDUs) have been characterized by high genetic multiplicity, suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full length gp160 gene obtained by single genome sequencing(SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence(IDU.CON). All the T/F virus was classified as subtype CRF07_BC, and predicted to be CCR5-tropic virus...
January 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28072889/in-depth-analysis-of-compartmentalization-of-hiv-1-matrix-protein-p17-in-pbmc-and-plasma
#14
Marina Selleri, Riccardo Dolcetti, Francesca Caccuri, Emanuela Giombini, Gabriella Rozera, Isabella Abbate, Alessia Mammone, Stefania Zanussi, Debora Martorelli, Simona Fiorentini, Arnaldo Caruso, Maria Rosaria Capobianchi
HIV-1 p17 plays an important role in the virus life-cycle and disease pathogenesis. Recent studies indicated a high heterogeneity of p17. A high number of insertions in the p17 carboxy-terminal region have been more frequently detected in patients with non-Hodgkin lymphoma (NHL), suggesting a role of altered p17 in lymphomagenesis. Based on p17 heterogeneity, possible PBMC/plasma compartmentalization of p17 variants was explored by ultra-deep pyrosequencing in five NHL patients. The high variability of p17 with insertions at the carboxy-terminal region was confirmed in plasma and observed for the first time in proviral genomes...
January 9, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28069446/rich2-is-implicated-in-viraemic-control-of-hiv-1-in-black-south-african-individuals
#15
Maria Paximadis, Refilwe N Ngqobe, Richard E Chaisson, Neil A Martinson, Caroline T Tiemessen
An intronic single nucleotide polymorphism (SNP) in RICH2 (rs2072255; 255(i)), in complete linkage disequilibrium (LD) with an exonic SNP (rs2072254; 254(e)), has been identified in a genome wide association study to be associated with progression to AIDS in Caucasian individuals. RICH2 links tetherin to the cortical actin network and the RICH2/tetherin interaction has been shown to be important for the downstream activation of NF-κβ and the consequential promotion of proinflammatory responses. We investigated the role of these two SNPs in natural control of HIV-1 in black South Africans including healthy controls (HCs; N=102) and antiretroviral-naive HIV-1-infected controllers (HICs; N=52) and progressors (N=74)...
January 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28069134/the-multifaceted-contributions-of-chromatin-to-hiv-1-integration-transcription-and-latency
#16
E De Crignis, T Mahmoudi
The capacity of the human immunodeficiency virus (HIV-1) to establish latent infections constitutes a major barrier to the development of a cure for HIV-1. In latent infection, replication competent HIV-1 provirus is integrated within the host genome but remains silent, masking the infected cells from the activity of the host immune response. Despite the progress in elucidating the molecular players that regulate HIV-1 gene expression, the mechanisms driving the establishment and maintenance of latency are still not fully understood...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28066922/x-ray-crystal-structure-of-the-n-terminal-region-of-moloney-murine-leukemia-virus-integrase-and-its-implications-for-viral-dna-recognition
#17
Rongjin Guan, Sriram Aiyer, Marie L Cote, Rong Xiao, Mei Jiang, Thomas B Acton, Monica J Roth, Gaetano T Montelione
The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain (CCD), and the C-terminal domain (CTD). The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1-44) and an HHCC zinc-finger NTD (residues 45-105), in two crystal forms are reported...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28065665/unbiased-identification-of-blood-based-biomarkers-for-pulmonary-tuberculosis-by-modeling-and-mining-molecular-interaction-networks
#18
Awanti Sambarey, Abhinandan Devaprasad, Abhilash Mohan, Asma Ahmed, Soumya Nayak, Soumya Swaminathan, George D'Souza, Anto Jesuraj, Chirag Dhar, Subash Babu, Annapurna Vyakarnam, Nagasuma Chandra
Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28062682/genome-wide-association-study-of-nevirapine-hypersensitivity-in-a-sub-saharan-african-hiv-infected-population
#19
Daniel F Carr, Stephane Bourgeois, Mas Chaponda, Louise Y Takeshita, Andrew P Morris, Elena M Cornejo Castro, Ana Alfirevic, Andrew R Jones, Daniel J Rigden, Sam Haldenby, Saye Khoo, David G Lalloo, Robert S Heyderman, Collet Dandara, Elizabeth Kampira, Joep J van Oosterhout, Francis Ssali, Paula Munderi, Giuseppe Novelli, Paola Borgiani, Matthew R Nelson, Arthur Holden, Panos Deloukas, Munir Pirmohamed
BACKGROUND: The antiretroviral nevirapine is associated with hypersensitivity reactions in 6%-10% of patients, including hepatotoxicity, maculopapular exanthema, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To undertake a genome-wide association study (GWAS) to identify genetic predisposing factors for the different clinical phenotypes associated with nevirapine hypersensitivity. METHODS: A GWAS was undertaken in a discovery cohort of 151 nevirapine-hypersensitive and 182 tolerant, HIV-infected Malawian adults...
January 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28061753/treatment-efficacy-of-azithromycin-1%C3%A2-g-single-dose-versus-doxycycline-100%C3%A2-mg-twice-daily-for-7%C3%A2-days-for-the-treatment-of-rectal-chlamydia-among-men-who-have-sex-with-men-a-double-blind-randomised-controlled-trial-protocol
#20
Andrew Lau, Fabian Kong, Christopher K Fairley, Basil Donovan, Marcus Chen, Catriona Bradshaw, Mark Boyd, Janaki Amin, Peter Timms, Sepehr Tabrizi, David G Regan, David A Lewis, Anna McNulty, Jane S Hocking
BACKGROUND: Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM...
January 6, 2017: BMC Infectious Diseases
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