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HIV genomics

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https://www.readbyqxmd.com/read/28440612/association-between-xrcc1-and-wrn-as-genetic-markers-of-stability-and-susceptibility-to-cancer-in-patients-with-hiv-aids-and-cancer-a-cross-sectional-study
#1
Gabriel de Carvalho Maldonado, Orlando Nascimento Terra Júnior, Adriano Arnóbio, Guilherme Rohem Alfradique, Maria Helena Ornellas, Roberto Irineu da Silva, Dirce Bonfim de Lima
Background: HIV-induced immunodeficiency has been implicated as a key factor for risk of cancer. Neoplasia is considered to result from accumulation of damage to the genome. Polymorphisms in repair genes, such as the XRCC1 and WRN, have been associated with susceptibility to development of cancer in patients with HIV/AIDS. The aim of this study was to analyze the frequency of polymorphisms in XRCC1 (Arg399Gln) and WRN (Cys1367Arg) in patients with HIV/AIDS with or without cancer. Materials and Methods: Genotyping for analysis of polymorphisms was carried out by PCR (Polymerase Chain Reaction) and RFLP (Restriction Fragment Length Polymorphism)...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28437703/antiviral-treatment-strategies-based-on-gene-silencing-and-genome-editing
#2
REVIEW
Roger Badia, Ester Ballana, José A Esté, Eva Riveira-Muñoz
The ability of some viruses to establish latently infected chronic reservoirs that escape to immune control becomes a major roadblock that impedes the cure of these infections. Therefore, new alternatives are needed to pursuit the eradication of viral persistent infections. Gene silencing technologies are in constant evolution and provide an outstanding sequence specificity that allows targeting any coding sequence of interest. Here we provide an overview of the development of gene silencing technologies ranging from initially RNA interference to the recently developed CRISPR/Cas9 and their potential as new antiviral strategies focusing on the eradication of HIV...
April 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28429755/opossum-apobec1-is-a-dna-mutator-with-retrovirus-and-retroelement-restriction-activity
#3
Terumasa Ikeda, Mayuko Shimoda, Diako Ebrahimi, John L VandeBerg, Reuben S Harris, Atsushi Koito, Kazuhiko Maeda
APOBEC3s (A3s) are single-stranded DNA cytosine deaminases that provide innate immune defences against retroviruses and mobile elements. A3s are specific to eutherian mammals because no direct homologs exist at the syntenic genomic locus in metatherian (marsupial) or prototherian (monotreme) mammals. However, the A3s in these species have the likely evolutionary precursors, the antibody gene deaminase AID and the RNA/DNA editing enzyme APOBEC1 (A1). Here, we used cell culture-based assays to determine whether opossum A1 restricts the infectivity of retroviruses including human immunodeficiency virus type 1 (HIV-1) and the mobility of LTR/non-LTR retrotransposons...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424288/virion-associated-vpr-alleviates-a-post-integration-block-to-hiv-1-infection-of-dendritic-cells
#4
Caitlin M Miller, Hisashi Akiyama, Luis M Agosto, Ann Emery, Chelsea R Ettinger, Ronald I Swamstrom, Andrew J Henderson, Suryaram Gummuluru
Viral protein R (Vpr) is an HIV-1 accessory protein whose function remains poorly understood. In this report, we sought to determine the requirement of Vpr in facilitating HIV-1 infection of monocyte-derived dendritic cells (MDDCs), one of the first cells to encounter virus in the peripheral mucosal tissues. We characterize in this report a significant restriction to Vpr-deficient virus replication and spread in MDDCs alone and in cell-to-cell spread in MDDC - CD4(+) T cell co-cultures. This restriction to HIV-1 replication in MDDCs was observed in a single round of virus replication and was rescued by expression of Vpr in trans in the incoming virion...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28416661/single-cell-analysis-of-hiv-1-transcriptional-activity-reveals-expression-of-proviruses-in-expanded-clones-during-art
#5
Ann Wiegand, Jonathan Spindler, Feiyu F Hong, Wei Shao, Joshua C Cyktor, Anthony R Cillo, Elias K Halvas, John M Coffin, John W Mellors, Mary F Kearney
Little is known about the fraction of human immunodeficiency virus type 1 (HIV-1) proviruses that express unspliced viral RNA in vivo or about the levels of HIV RNA expression within single infected cells. We developed a sensitive cell-associated HIV RNA and DNA single-genome sequencing (CARD-SGS) method to investigate fractional proviral expression of HIV RNA (1.3-kb fragment of p6, protease, and reverse transcriptase) and the levels of HIV RNA in single HIV-infected cells from blood samples obtained from individuals with viremia or individuals on long-term suppressive antiretroviral therapy (ART)...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414762/transcriptional-networks-are-associated-with-resistance-to-mycobacterium-tuberculosis-infection
#6
Chetan Seshadri, Nafiseh Sedaghat, Monica Campo, Glenna Peterson, Richard D Wells, Gregory S Olson, David R Sherman, Catherine M Stein, Harriet Mayanja-Kizza, Ali Shojaie, W Henry Boom, Thomas R Hawn
RATIONALE: Understanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases, such as HIV. OBJECTIVES: To compare the early transcriptional response of M.tb-infected monocytes between Ugandan household contacts of tuberculosis patients who demonstrate clinical resistance to M.tb infection (cases) and matched controls with latent tuberculosis infection. METHODS: Cases (n = 10) and controls (n = 18) were selected from a long-term household contact study in which cases did not convert their tuberculin skin test (TST) or develop tuberculosis over two years of follow up...
2017: PloS One
https://www.readbyqxmd.com/read/28412523/progenitor-strain-introduction-of-mycobacterium-bovis-at-the-wildlife-livestock-interface-can-lead-to-clonal-expansion-of-the-disease-in-a-single-ecosystem
#7
Anzaan Dippenaar, Sven David Charles Parsons, Michele Ann Miller, Tiny Hlokwe, Nicolaas Claudius Gey van Pittius, Sabir Abdu Adroub, Abdallah Musa Abdallah, Arnab Pain, Robin Mark Warren, Anita Luise Michel, Paul David van Helden
Mycobacterium bovis infects multiple wildlife species and domesticated cattle across South Africa, and negatively impacts on livestock trade and movement of wildlife for conservation purposes. M. bovis infection was first reported in the Kruger National Park (KNP) in South Africa during the 1990s, and has since spread to infect numerous animal host species throughout the park and across South Africa. Whole genome sequencing data of 17 M. bovis isolates were analyzed to investigate the genomic diversity among M...
April 13, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28408207/transactivator-protein-an-alternative-for-delivery-of-recombinant-proteins-for-safer-reprogramming-of-induced-pluripotent-stem-cell
#8
REVIEW
Fazlina Nordin, Raja Norazireen Raja Ahmad, Farzin Farzaneh
Induced pluripotent stem cells (iPSC) are somatic cells reprogrammed to pluripotency by forced expression of pluripotency factors. These cells are shown to have the same pluripotent potential as embryonic stem cells (ESC) and considered as an alternative to the much controversial usage of ESC which involved human embryos. However, the traditional method in reprogramming cells into iPSC using genome-integrating retro- or lenti- viruses remains an obstacle for its application in clinical setting. Although numerous studies have been conducted for a safer DNA-based reprogramming, reprogramming of iPSC by genetic modifications may raise the possibility of malignant transformation and has been a major limitation for its usage in clinical applications...
April 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28404672/increased-tuberculosis-patient-mortality-associated-with-mycobacterium-tuberculosis-mutations-conferring-resistance-to-second-line-antituberculous-drugs
#9
Sophia B Georghiou, Marva Seifert, Donald G Catanzaro, Richard S Garfein, Timothy C Rodwell
Rapid molecular diagnostics have great potential to limit the spread of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis (Mtb) genome that confer phenotypic drug resistance. However, there is little data published regarding the relationships between the detected Mtb resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between Mtb resistance mutations and patient mortality...
April 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28403241/characterization-of-a-novel-hiv-1-unique-recombinant-form-between-crf07_bc-and-crf55_01b-in-men-who-have-sex-with-men-in-guangzhou-china
#10
Yue Wu, Xuqi Ren, Dan Yin, Haiying Wang, Zhengwei Wan, Xiufen Li, Guifang Hu, Shixing Tang
Here, we report the genetic diversity of HIV-1 and emergence of novel HIV-1 unique recombinant forms (URF) in both HIV-infected intravenous drug users (IDU) and men who have sex with men (MSM) in Guangzhou, China. We further characterized a novel URF strain isolated from an HIV-infected MSM, GD698. Near full-length genome (NFLG) phylogenic analysis showed that this novel URF was composed of CRF07_BC and CRF55_01B, with two recombinant breakpoints (nt 6,003 and 8,251 relative to the HXB2 genome) in the vpu/env and env genes, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28402970/the-genotyping-resistance-profile-of-the-pol-gene-detected-in-blood-of-newly-diagnosed-hiv-positive-men-is-durably-archived-in-the-gut-whatever-the-time-of-initiation-of-cart
#11
Anne Emmanuelle Depincé, Elodie Dussert, Delphine Vergnon-Miszczycha, Abdelaye Keita, Sylvie Pillet, Elisabeth Botelho-Nevers, Anne Frésard, Amandine Gagneux-Brunon, Frédéric R Lucht, Xavier Roblin, Bruno Pozzetto, Stéphane Paul, Thomas Bourlet
OBJECTIVE: To evaluate the mutational patterns on the pol gene of the main HIV-1 strain archived in cell genome of 10 chronically infected men according to their clinical and therapeutic history. The genotyping resistance profiles were compared between the first blood plasma available at the time of HIV diagnosis and rectal biopsies and PBMC sampled 1-5 years after the initiation of combined antiretroviral therapy (cART). METHODS: HIV-1 RNA and cell-associated HIV-1 DNA were quantified by Abbott Real-Time HIV-1 and Generic HIV® DNA cell (Biocentric) assays...
April 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28399968/tuberculosis-resistance-conferring-mutations-with-fitness-cost-among-hiv-positive-individuals-in-uganda
#12
W Ssengooba, D Lukoye, C J Meehan, D P Kateete, M L Joloba, B C de Jong, F G Cobelens, F van Leth
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is considered to be less transmissible due to the fitness cost associated with drug resistance-conferring mutations in essential genes. OBJECTIVE: To test the hypothesis that TB drug resistance-conferring mutations with fitness cost are more frequent among human immunodeficiency virus (HIV) positive than among HIV-negative patients. DESIGN: We analysed all strains from the two TB drug resistance surveys conducted in Uganda between 2008 and 2011...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28399797/a-machine-learning-approach-for-viral-genome-classification
#13
Mohamed Amine Remita, Ahmed Halioui, Abou Abdallah Malick Diouara, Bruno Daigle, Golrokh Kiani, Abdoulaye Baniré Diallo
BACKGROUND: Advances in cloning and sequencing technology are yielding a massive number of viral genomes. The classification and annotation of these genomes constitute important assets in the discovery of genomic variability, taxonomic characteristics and disease mechanisms. Existing classification methods are often designed for specific well-studied family of viruses. Thus, the viral comparative genomic studies could benefit from more generic, fast and accurate tools for classifying and typing newly sequenced strains of diverse virus families...
April 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28398773/genetic-characterization-of-a-unique-recombinant-strain-identified-in-yunnan-with-genome-comprised-of-b-and-c
#14
Xiaolin Wang, Min Zhang, Jianjian Li, Tianyi Li, Changrong Sun, Hanping Li, Yongjian Liu, Siyang Liu, Daomin Zhuang, Zuoyi Bao, Jingwan Han, Jingyun Li, Lin Li
Since the first identification of HIV-1 outbreak in Dehong, Yunnan province has been the epidemic center of HIV in China. Due to the special geographic location and the frequent population mobility, Yunnan province contained complex HIV subtype distribution. Many new CRFs and URFs have been found in recently years. In this study, a unique HIV-1 recombinant strain (URF) genome (YN10134) was characterized from an HIV-positive female in Yunnan, China. This virus genome had a complex intersubtype recombinant structure with 8 breakpoints, composed of subtype B and subtype C...
February 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28388302/genome-wide-association-and-replication-study-of-hepatotoxicity-induced-by-antiretrovirals-alone-or-with-concomitant-anti-tuberculosis-drugs
#15
Zelalem Petros, Ming Ta Michael Lee, Atsushi Takahashi, Yanfei Zhang, Getnet Yimer, Abiy Habtewold, Ina Schuppe-Koistinen, Taisei Mushiroda, Eyasu Makonnen, Michiaki Kubo, Eleni Aklillu
Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients...
April 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28385843/draft-genome-sequence-of-mycobacterium-colombiense
#16
Amar Bouam, Catherine Robert, Anthony Levasseur, Michel Drancourt
Mycobacterium colombiense is a rapidly growing mycobacterium initially isolated from the blood of an HIV-positive patient in Colombia. Its 5,854,893-bp draft genome exhibits a G+C content of 67.64%, 5,233 protein-coding genes, and 54 predicted RNA genes.
April 6, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28381579/reverse-transcription-mechanically-initiates-hiv-1-capsid-disassembly
#17
Sanela Rankovic, Janani Varadarajan, Ruben Ramalho, Christopher Aiken, Itay Rousso
The HIV-1 core consists of the viral genomic RNA and several viral proteins encased within a conical capsid. Following cell entry, the core disassembles in a process termed uncoating. Although HIV-1 uncoating has been linked to reverse transcription of the viral genome in target cells, the mechanism by which uncoating is initiated is unknown. Using time-lapse atomic force microscopy, we analyzed the morphology and physical properties of isolated HIV-1 cores during the course of reverse transcription in vitro We find that, during an early stage of reverse transcription the pressure inside the capsid increases, reaching a maximum after 7 hours...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28381554/dna-mutagenic-activity-and-capacity-for-hiv-1-restriction-of-the-cytidine-deaminase-apobec3g-depends-on-whether-dna-or-rna-binds-to-tyrosine-315
#18
Bogdan Polevoda, Rebecca Joseph, Alan E Friedman, Ryan P Bennett, Rebecca Greiner, Thareendra De Zoysa, Ryan A Stewart, Harold C Smith
APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) that bind to nucleic acids. A3G mutates the HIV genome by deamination of dC to dU, leading to accumulation of virus-inactivating mutations. Binding to cellular RNAs inhibits A3G binding to substrate single-stranded (ss) DNA and CDA activity. RNA and ssDNA bind to the same three A3G tryptic peptides (amino acids 181-194, 314-320, and 345-374) that form parts of a continuously exposed protein surface extending from the catalytic domain in the C-terminus of A3G to its N-terminus...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28379444/a-dead-box-protein-acts-through-rna-to-promote-hiv-1-rev-rre-assembly
#19
Rajan Lamichhane, John A Hammond, Raymond F Pauszek, Rae M Anderson, Ingemar Pedron, Edwin van der Schans, James R Williamson, David P Millar
The HIV-1 Rev protein activates nuclear export of unspliced and partially spliced viral RNA transcripts, which encode the viral genome and the genes encoding viral structural proteins, by binding to and oligomerizing on the Rev Response Element (RRE). The human DEAD-box protein 1 (DDX1) enhances the RNA export activity of Rev through an unknown mechanism. Using a single-molecule assembly assay and various DDX1 mutants, we show that DDX1 acts through the RRE RNA to specifically accelerate the nucleation step of the Rev-RRE assembly process...
March 31, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28379346/a-penalized-regression-approach-to-haplotype-reconstruction-of-viral-populations-arising-in-early-hiv-siv-infection
#20
Sivan Leviyang, Igor Griva, Sergio Ita, Welkin E Johnson
Motivation: Next generation sequencing (NGS) has been increasingly applied to characterize viral evolution during HIV and SIV infections. In particular, NGS datasets sampled during the initial months of infection are characterized by relatively low levels of diversity as well as convergent evolution at multiple loci dispersed across the viral genome. Consequently, fully characterizing viral evolution from NGS datasets requires haplotype reconstruction across large regions of the viral genome...
April 4, 2017: Bioinformatics
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