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HIV genomics

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https://www.readbyqxmd.com/read/29683851/detection-of-numerous-hiv-1-mo-recombinants-in-france
#1
Fabienne De Oliveira, Pierre Cappy, Véronique Lemée, Alice Moisan, Charlotte Pronier, Laurence Bocket, Magali Bouvier-Alias, Marie-Laure Chaix, Elyanne Gault, Odile Morvan, Jean-Dominique Poveda, Véronique Schneider, Marc Wirden, Elodie Alessandri-Gradt, Thomas Mourez, Jean-Christophe Plantier
BACKGROUND: The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29683841/monotypic-low-level-hiv-viremias-during-art-are-associated-with-disproportionate-production-of-x4-virions-and-systemic-immune-activation
#2
Marta E Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams-Wietzikoski, Jillian Legard, Jennifer Mckernan-Mullin, Kelli Kraft, Frankline Onchiri, Joshua Stern, Sarah Holte, Kevin J Ryan, Edward P Acosta, Alberto La Rosa, Robert W Coombs, Eduardo Ticona, Lisa M Frenkel
OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naïve Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29677208/modeling-the-dynamics-and-kinetics-of-hiv-1-gag-during-viral-assembly
#3
Michael D Tomasini, Daniel S Johnson, Joshua S Mincer, Sanford M Simon
We report a computational model for the assembly of HIV-1 Gag into immature viral particles at the plasma membrane. To reproduce experimental structural and kinetic properties of assembly, a process occurring on the order of minutes, a coarse-grained representation consisting of a single particle per Gag molecule is developed. The model uses information relating the functional interfaces implicated in Gag assembly, results from cryo electron-tomography, and biophysical measurements from fluorescence microscopy, such as the dynamics of Gag assembly at single virions...
2018: PloS One
https://www.readbyqxmd.com/read/29673219/hiv-tat-p-tefb-interaction-a-potential-target-for-novel-anti-hiv-therapies
#4
REVIEW
Kaori Asamitsu, Koh Fujinaga, Takashi Okamoto
Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb)...
April 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29672607/infant-transmitted-founder-hiv-1-viruses-from-peripartum-transmission-are-neutralization-resistant-to-paired-maternal-plasma
#5
Amit Kumar, Claire E P Smith, Elena E Giorgi, Joshua Eudailey, David R Martinez, Karina Yusim, Ayooluwa O Douglas, Lisa Stamper, Erin McGuire, Celia C LaBranche, David C Montefiori, Genevieve G Fouda, Feng Gao, Sallie R Permar
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29669733/evolution-of-dnaasei-hypersensitive-sites-in-mhc-regulatory-regions-of-primates
#6
Yabin Jin, Rachel M Gittelman, Yueer Lu, Xiaohui Liu, Ming D Li, Fei Ling, Joshua M Akey
It has been challenged to determine the disease-causing variant(s) for most major histocompatibility complex (MHC) associated diseases. However, it is becoming increasingly clear that regulatory variation is pervasive and a fundamentally important mechanism governing phenotypic diversity and disease susceptibility. We leveraged DNase I data from 136 human cells to characterize the regulatory landscape of the MHC region, including 4867 DNase I hypersensitive sites (DHSs). We identified thousands of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence...
April 18, 2018: Genetics
https://www.readbyqxmd.com/read/29667040/management-of-superficial-and-deep-seated-staphylococcus-aureus-skin-and-soft-tissue-infections-in-sub-saharan-africa-a-post-hoc-analysis-of-the-staphnet-cohort
#7
Abraham Alabi, Theckla Kazimoto, Marthe Lebughe, Delfino Vubil, Patrick Phaku, Inacio Mandomando, Winfried V Kern, Salim Abdulla, Alexander Mellmann, Lena Peitzmann, Markus Bischoff, Georg Peters, Mathias Herrmann, Martin P Grobusch, Frieder Schaumburg, Siegbert Rieg
PURPOSE: The incidence of Staphylococcus aureus skin and soft tissue infection (SSTI) is high in sub-Saharan Africa. This is fueled by a high prevalence of Panton-Valentine leukocidin (PVL), which can be associated with necrotizing disease. The aim was to describe the clinical presentation and the treatment of SSTI in the African setting and to identify challenges in the management. METHODS: Patients (n = 319) were recruited in DR Congo (n = 56, 17.6%), Gabon (n = 89, 27...
April 17, 2018: Infection
https://www.readbyqxmd.com/read/29666343/interleukin-gene-polymorphisms-and-susceptibility-to-hiv-1-infection-a-meta-analysis
#8
Chrissa G Tsiara, Georgios K Nikolopoulos, Niki L Dimou, Katerina G Pantavou, Pantelis G Bagos, Benedicta Mensah, Michael Talias, Georgia G Braliou, Dimitra Paraskeva, Stefanos Bonovas, Angelos Hatzakis
Some subjects are repeatedly exposed to human immunodeficiency virus (HIV), yet they remain uninfected. This suggests the existence of host-resistance mechanisms. The current study synthesizes the evidence regarding the association between interleukin (IL) gene polymorphisms and HIV susceptibility. Medline, Scopus and the Web of Science databases were systematically searched, and a meta-analysis of case-control studies was conducted. Univariate and bivariate methods were used. The literature search identified 42 eligible studies involving 15,727 subjects...
March 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29666292/human-immunodeficiency-virus-tat-protein-aids-v-region-somatic-hypermutation-in-human-b-cells
#9
Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D Scharff
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29664957/killer-cell-immunoglobulin-like-receptors-associate-with-hiv-1-infection-in-a-narrow-source-han-chinese-cohort
#10
Linghang Wang, Yonghong Zhang, Keyi Xu, Tao Dong, Sarah Rowland-Jones, Louis-Marie Yindom
BACKGROUND: The HIV pandemic remains the most serious challenge to public health worldwide. The hallmark characteristics of the disease is the eventual failure of the immune system to control opportunistic infections and death. However not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART)...
2018: PloS One
https://www.readbyqxmd.com/read/29664940/identifying-the-assembly-intermediate-in-which-gag-first-associates-with-unspliced-hiv-1-rna-suggests-a-novel-model-for-hiv-1-rna-packaging
#11
Brook C Barajas, Motoko Tanaka, Bridget A Robinson, Daryl J Phuong, Kasana Chutiraka, Jonathan C Reed, Jaisri R Lingappa
During immature capsid assembly, HIV-1 genome packaging is initiated when Gag first associates with unspliced HIV-1 RNA by a poorly understood process. Previously, we defined a pathway of sequential intracellular HIV-1 capsid assembly intermediates; here we sought to identify the intermediate in which HIV-1 Gag first associates with unspliced HIV-1 RNA. In provirus-expressing cells, unspliced HIV-1 RNA was not found in the soluble fraction of the cytosol, but instead was largely in complexes ≥30S. We did not detect unspliced HIV-1 RNA associated with Gag in the first assembly intermediate, which consists of soluble Gag...
April 17, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29664930/distinctive-variation-in-the-u3r-region-of-the-5-long-terminal-repeat-from-diverse-hiv-1-strains
#12
Christelle Mbondji-Wonje, Ming Dong, Xue Wang, Jiangqin Zhao, Viswanath Ragupathy, Ana M Sanchez, Thomas N Denny, Indira Hewlett
Functional mapping of the 5'LTR has shown that the U3 and the R regions (U3R) contain a cluster of regulatory elements involved in the control of HIV-1 transcription and expression. As the HIV-1 genome is characterized by extensive variability, here we aimed to describe mutations in the U3R from various HIV-1 clades and CRFs in order to highlight strain specific differences that may impact the biological properties of diverse HIV-1 strains. To achieve our purpose, the U3R sequence of plasma derived virus belonging to different clades (A1, B, C, D, F2) and recombinants (CRF02_AG, CRF01_AE and CRF22_01A1) was obtained using Illumina technology...
2018: PloS One
https://www.readbyqxmd.com/read/29663494/phylogenetic-analysis-of-htlv-1-in-iranian-blood-donors-hiv-1-positive-patients-and-patients-with-beta-thalassemia
#13
Leila Pirayeshfard, Zohreh Sharifi, Sedigheh Amini-Kafiabad, Nasrin Haghnazari Sadaghiani
BACKGROUND: Human T-cell leukemia virus (HTLV) has been associated with various disease types. Since the discovery of the virus in 1980, seven subtypes of the virus have been identified. HTLV is widespread and endemic in some regions, such as Japan, Africa, South America, and northeast Iran. This study aimed to identify HTLV-1 genotype and also to analyze the nucleotide sequence of the LTR region in three groups, including blood donors, HIV-1+ patients, and β-thalassemia patients. MATERIALS AND METHODS: In this cross-sectional study, 2200 samples were collected from blood donors in Tehran (2000 samples), HIV-1+ patients (100 samples) and β-thalassemia patients (100 samples)...
April 16, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29658309/individuals-with-hiv-1-subtype-c-infection-and-cryptococcal-meningitis-exhibit-viral-genetic-intermixing-of-hiv-1-between-plasma-and-cerebrospinal-fluid-and-a-high-prevalence-of-cxcr4-using-variants
#14
Katlego Sojane, Richard T Kangethe, Christina C Chang, Mahomed-Yunus Moosa, Sharon Ruth Lewin, Martyn A French, Thumbi Ndung'u
The genotypic properties of HIV-1 subtype C in individuals presenting with cryptococcal meningitis (CM) are not well established. Employing single-genome amplification as well as bulk PCR, cloning and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C env in 16 antiretroviral therapy naïve study participants with CM. Eleven of the 16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated, with the rest having either a plasma or CSF sample evaluated. Before antiretroviral therapy initiation, matched plasma and cerebrospinal fluid-derived env sequences of all 11 participants displayed genetic intermixing between the two compartments...
April 15, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29651274/identification-of-unequally-represented-founder-viruses-among-tissues-in-very-early-siv-rectal-transmission
#15
Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wan, Jianqing Xu
Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50 ) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29649444/single-hiv-1-imaging-reveals-progression-of-infection-through-ca-dependent-steps-of-docking-at-the-nuclear-pore-uncoating-and-nuclear-transport
#16
Ashwanth C Francis, Gregory B Melikyan
The HIV-1 core consists of capsid proteins (CA) surrounding viral genomic RNA. After virus-cell fusion, the core enters the cytoplasm and the capsid shell is lost through uncoating. CA loss precedes nuclear import and HIV integration into the host genome, but the timing and location of uncoating remain unclear. By visualizing single HIV-1 infection, we find that CA is required for core docking at the nuclear envelope (NE), whereas early uncoating in the cytoplasm promotes proteasomal degradation of viral complexes...
April 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29649127/gene-therapy-for-chronic-hbv-can-we-eliminate-cccdna
#17
REVIEW
Kristie Bloom, Mohube Betty Maepa, Abdullah Ely, Patrick Arbuthnot
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions...
April 12, 2018: Genes
https://www.readbyqxmd.com/read/29643844/emerging-roles-of-n-6-methyladenosine-on-hiv-1-rna-metabolism-and-viral-replication
#18
REVIEW
Sebastián Riquelme-Barrios, Camila Pereira-Montecinos, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
N6 -methyladenosine (m6 A) is the most abundant internal modification present in Eukaryotic mRNA. The functions of this chemical modification are mediated by m6 A-binding proteins (m6 A readers) and regulated by methyltransferases (m6 A writers) and demethylases (m6 A erasers), which together are proposed to be responsible of a new layer of post-transcriptional control of gene expression. Despite the presence of m6 A in a retroviral genome was reported more than 40 years ago, the recent development of sequencing-based technologies allowing the mapping of m6 A in a transcriptome-wide manner made it possible to identify the topology and dynamics of m6 A during replication of HIV-1 as well as other viruses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29643241/truncated-cpsf6-forms-higher-order-complexes-that-bind-and-disrupt-hiv-1-capsid
#19
Jiying Ning, Zhou Zhong, Douglas K Fischer, Gemma Harris, Simon C Watkins, Zandrea Ambrose, Peijun Zhang
Cleavage and polyadenylation specificity factor 6 (CPSF6) is a human protein that binds HIV-1 capsid and mediates nuclear transport and integration targeting of HIV-1 pre-integration complexes. Truncation of the protein at its C-terminal nuclear-targeting arginine/serine-rich (RS-) domain produces a protein, CPSF6-358, that potently inhibits HIV-1 infection by targeting the capsid and inhibiting nuclear entry. To understand the molecular mechanism behind this restriction, the interaction between CPSF6-358 and HIV-1 capsid was characterized using in vitro and in vivo assays...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29625148/genome-scale-screening-identification-of-sacas9-grnas-for-targeting-hiv-1-provirus-and-suppression-of-hiv-1-infection
#20
Qiankun Wang, Shuai Liu, Zhepeng Liu, Zunhui Ke, Chunmei Li, Xiao Yu, Shuliang Chen, Deyin Guo
The CRISPR/Cas9 gene-editing approach has been widely used in anti-HIV-1 gene therapy research. However, the major challenges facing the therapeutic application of CRISPR/Cas9 are the precise genome cleavage efficacy and efficient delivery of Cas9/gRNA specifically to the HIV-infected cells. Recently, a small size Cas9 from Staphylococcus aureus (SaCas9) has shown promise in genome editing in eukaryotic cells, suggesting a potential usage in blocking HIV-1 infection by targeting the HIV-1 genome. Here, we designed 43 guide RNAs (gRNAs) against the HIV-1 genome, thereby identifying 8 gRNAs that efficiently and specifically disrupt the target DNA by SaCas9...
April 3, 2018: Virus Research
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