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HIV genomics

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https://www.readbyqxmd.com/read/28642469/tracing-the-epidemic-history-of-hiv-1-crf01_ae-clusters-using-near-complete-genome-sequences
#1
Xingguang Li, Haizhou Liu, Lu Liu, Yi Feng, Marcia L Kalish, Simon Y W Ho, Yiming Shao
Human immunodeficiency virus (HIV) has a number of circulating recombinant forms that are the product of recombination between different HIV subtypes. The first circulating recombinant form of HIV-1 to be identified was CRF01_AE, which originated in Central Africa and is now most prevalent in Southeast and East Asia. In this study, we investigated the timescale, evolutionary history, and population genetics of the HIV-1 CRF01_AE strains primarily responsible for the epidemic in Asia. A further aim of our study was to define and standardize the nomenclature and provide well-characterized reference sequences for the phylogenetic transmission clusters of CRF01_AE...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#2
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28633446/genetic-indicators-of-drug-resistance-in-the-highly-repetitive-genome-of-trichomonas-vaginalis
#3
Martina Bradic, Sally D Warring, Grace E Tooley, Paul Scheid, William E Secor, Kirkwood M Land, Po-Jung Huang, Ting-Wen Chen, Chi-Ching Lee, Petrus Tang, Steven A Sullivan, Jane M Carlton
Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance...
June 19, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28628667/characterization-of-hiv-1-crf90_bf1-and-putative-novel-crfs_bf1-in-central-west-north-and-northeast-brazilian-regions
#4
Mônica Nogueira da Guarda Reis, Gonzalo Bello, Monick Lindenmeyer Guimarães, Mariane Martins Araújo Stefani
The Brazilian AIDS epidemic has been characterized by an increasing rate of BF1 recombinants and so far eight circulating recombinant forms/CRFs_BF1 have been described countrywide. In this study, pol sequences (protease/PR, reverse transcriptase/RT) of 87 BF1 mosaic isolates identified among 828 patients living in six Brazilian States from three geographic regions (Central West, North, Northeast) were analyzed. Phylogenetic and bootscan analyses were performed to investigate the evolutionary relationship and mosaic structure of BF1 isolates...
2017: PloS One
https://www.readbyqxmd.com/read/28628665/a-chromosome-5q31-1-locus-associates-with-tuberculin-skin-test-reactivity-in-hiv-positive-individuals-from-tuberculosis-hyper-endemic-regions-in-east-africa
#5
Rafal S Sobota, Catherine M Stein, Nuri Kodaman, Isaac Maro, Wendy Wieland-Alter, Robert P Igo, Albert Magohe, LaShaunda L Malone, Keith Chervenak, Noemi B Hall, Mecky Matee, Harriet Mayanja-Kizza, Moses Joloba, Jason H Moore, William K Scott, Timothy Lahey, W Henry Boom, C Fordham von Reyn, Scott M Williams, Giorgio Sirugo
One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628034/clonal-expansion-of-genome-intact-hiv-1-in-functionally-polarized-th1-cd4-t-cells
#6
Guinevere Q Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D Walker, Eric S Rosenberg, Xu G Yu, Mathias Lichterfeld
HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625133/recent-advances-in-targeting-the-hiv-1-tat-tar-complex
#7
Fardokht A Abulwerdi, Stuart F J Le Grice
Following seminal discoveries by Rosen and co-workers in 1985, the HIV-1 TAR has emerged as one of the most extensively studied regulatory elements of the HIV-1 genome. Located adjacent to the long terminal repeat promoter, this cis-acting motif, in conjunction with the viral Tat protein, plays a critical role in viral genomic RNA synthesis via modification of the transcription complex. As such, the Tat/TAR axis has been the subject of intense efforts aimed at developing therapeutic interventions, directed against both the protein and nucleic acid components...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28623276/gag-protease-coevolution-analyses-define-novel-structural-surfaces-in-the-hiv-1-matrix-and-capsid-involved-in-resistance-to-protease-inhibitors
#8
Francisco M Codoñer, Ruth Peña, Oscar Blanch-Lombarte, Esther Jimenez-Moyano, Maria Pino, Thomas Vollbrecht, Bonaventura Clotet, Javier Martinez-Picado, Rika Draenert, Julia G Prado
Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622640/clinical-course-and-core-variability-in-hbv-infected-patients-without-detectable-anti-hbc-antibodies
#9
Olympia E Anastasiou, Marek Widera, Jens Verheyen, Johannes Korth, Guido Gerken, Fabian A Helfritz, Ali Canbay, Heiner Wedemeyer, Sandra Ciesek
BACKGROUND: The presence of anti-HBc antibodies indicates direct encounter of the immune system with hepatitis B virus (HBV). OBJECTIVES: Aim of our study was to seek for anti-HBc negative but HBV replicating patients and analyze their clinical course and preconditions. STUDY DESIGN: From 1568 HBV-DNA positive patients, 29 patients (1.85%) tested negative for anti-HBc. The absence of anti-HBc could be confirmed in 19 patients using an alternative assay...
June 8, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28618736/frequency-of-human-parvovirus-4-parv4-viremia-among-hbv-infected-patients-and-healthy-donors-in-shiraz-iran
#10
Fereshte Amirahmadi, Jamal Sarvari, Seyed Younes Hosseini, Neda Pirbonyeh, Ali Akbar Gorzin
BACKGROUND/AIM: PARV4, a small DNA virus belonging to the family Parvoviridae, was first isolated in an HBV injecting drug user. Several studies have investigated PARV4 co-infection with HBV and HCV and its effect on the progression of liver disease. The aim of this study was to determine the frequency of PARV4 among HBV-infected patients and healthy individuals. MATERIALS AND METHODS: A group of 90 HBV patients and a group of 90 healthy subjects were included in this study...
June 12, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28615212/conserved-v%C3%AE-1-binding-geometry-in-a-setting-of-locus-disparate-phla-recognition-by-%C3%AE-%C3%AE-%C3%AE-tcrs-insight-into-recognition-of-hiv-peptides-by-tcr
#11
Yi Shi, Ai Kawana-Tachikawa, Feng Gao, Jianxun Qi, Chuansheng Liu, Jia Gao, Hao Cheng, Takamasa Ueno, Aikichi Iwamoto, George F Gao
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments, to form classical γδTCR or uncommon αβTCR using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615207/allosteric-hiv-1-integrase-inhibitors-lead-to-premature-degradation-of-the-viral-rna-genome-and-integrase-in-target-cells
#12
Michaela K Madison, Dana Q Lawson, Jennifer Elliott, Ayşe Naz Ozantürk, Pratibha C Koneru, Dana Townsend, Manel Errando, Mamuka Kvaratskhelia, Sebla B Kutluay
Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles, in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice. These particles are non-infectious and blocked at an early reverse transcription stage in target cells. However, the basis of this reverse transcription defect is unknown. Here we show that the viral RNA genome and IN from ALLINI-treated virions are prematurely degraded in target cells, whereas reverse transcriptase remains active and stably associated with the capsid lattice...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614360/comparative-genomics-of-cryptococcus-neoformans-var-grubii-associated-with-meningitis-in-hiv-infected-and-uninfected-patients-in-vietnam
#13
Jeremy N Day, Seet Qihui, Lam Tuan Thanh, Phan Hai Trieu, Anh Duong Van, Nha Hoang Thu, Tran Thi Hong Chau, Nguyen P H Lan, Nguyen Van Vinh Chau, Philip M Ashton, Guy E Thwaites, Maciej F Boni, Marcel Wolbers, Niranjan Nagarajan, Patrick B O Tan, Stephen Baker
The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients...
June 14, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28611493/construction-selection-and-immunogenicity-of-recombinant-fowlpox-candidate-vaccine-co-expressing-hiv-1-gag-and-gp145
#14
Yilong Zhu, Yan Guo, Shouwen Du, Cunxia Liu, Maopeng Wang, Dayong Ren, Fei Zhao, Yanfang Zhang, Wenchao Sun, Yiquan Li, Tingting Cao, Yingyue Jiang, Bin Xing, Bing Bai, Chang Li, Ningyi Jin
An HIV candidate vaccine for the Chinese population was designed by constructing a recombinant fowlpox virus expressing HIV-1 gag and HIV gp145 proteins via homologous recombination and plaque screening using enhanced green fluorescent protein (EGFP) as the reporter gene. EGFP in the recombinant was then knocked out with the Cre/Loxp system yielding rFPVHg-Hp, which was identified at the genomic, transcriptional and translational levels. The immunogenicity of rFPVHg-Hp was analyzed by measuring levels of HIV-specific antibodies and IFN-γ-secreting splenocytes by enzyme-linked immunosorbent assay and IFN enzyme-linked immune spot test in the BALB/c mouse model...
June 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/28610923/l368f-v408f-double-mutant-of-ibd-of-ledgf-p75-retains-interaction-with-m178i-mutant-of-hiv-1-integrase
#15
Anu George, Nidhanapati K Raghavendra
Lens-epithelium-derived-growth factor (LEDGF/p75) is an essential host protein for integration of HIV-1 DNA into host genome. Earlier alanine scanning mutational analysis has revealed that residues I365, D366 and F406 in the integrase binding domain (IBD) of p75 are critical for interaction with HIV-1 integrase (IN), while K364, V408 have intermediate effect and residues N367, L368, R405, K407 show wild type binding with IN. To gain insight into contribution of side chains of L368 and V408 that are adjacent to critical residues I365 and F406, respectively, site directed mutation of these residues to Ile/Leu, Met and Phe has been performed and characterized in this study...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28608842/talaromyces-marneffei-genomic-transcriptomic-proteomic-and-metabolomic-studies-reveal-mechanisms-for-environmental-adaptations-and-virulence
#16
REVIEW
Susanna K P Lau, Chi-Ching Tsang, Patrick C Y Woo
Talaromycesmarneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus...
June 13, 2017: Toxins
https://www.readbyqxmd.com/read/28606917/quantitative-temporal-viromics-of-an-inducible-hiv-1-model-yields-insight-to-global-host-targets-and-phospho-dynamics-associated-with-vpr
#17
John D Lapek, Mary K Lewinski, Jacob M Wozniak, John Guatelli, David J Gonzalez
The mechanisms by which human immunodeficiency virus (HIV) circumvents and coopts cellular machinery to replicate and persist in cells are not fully understood. HIV accessory proteins play key roles in the HIV life cycle by altering host pathways that are often dependent on post-translational modifications (PTMs). Thus, the identification of HIV accessory protein host targets and their PTM status is critical to fully understand how HIV invades, avoids detection and replicates to spread infection. To date, a comprehensive characterization of HIV accessory protein host targets and modulation of their PTM status does not exist...
June 12, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28604782/viral-genetic-variation-accounts-for-a-third-of-variability-in-hiv-1-set-point-viral-load-in-europe
#18
François Blanquart, Chris Wymant, Marion Cornelissen, Astrid Gall, Margreet Bakker, Daniela Bezemer, Matthew Hall, Mariska Hillebregt, Swee Hoe Ong, Jan Albert, Norbert Bannert, Jacques Fellay, Katrien Fransen, Annabelle J Gourlay, M Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F Günthard, Pia Kivelä, Roger Kouyos, Oliver Laeyendecker, Kirsi Liitsola, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Guido Vanham, Ben Berkhout, Paul Kellam, Peter Reiss, Christophe Fraser
HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%)...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28596938/genome-edited-t-cell-therapies
#19
REVIEW
Juliette M K M Delhove, Waseem Qasim
PURPOSE OF REVIEW: Alternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28591079/genetic-analyses-of-hiv-env-associated-with-uveitis-in-antiretroviral-na%C3%A3-ve-individuals
#20
Corey A Williams-Wietzikoski, Isaac D So, Marta E Bull, Tanawan Samleerat, Kessara Pathanapitoon, Paradee Kunavisarut, Natedao Kongyai, Nicole Ngo-Giang-Huong, Lisa M Frenkel, Wasna Sirirungsi
OBJECTIVE: To analyze and compare human immunodeficiency virus type-1 (HIV) env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease. DESIGN: A prospective case series of five HIV-infected antiretroviral (ARV)-naïve individuals with uveitis negative for other pathogens. METHODS: RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers...
June 6, 2017: AIDS
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