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HIV genomics

Yasmin Abo-Zeid, Richard A Urbanowicz, Brian J Thomson, William L Irving, Alexander W Tarr, Martin C Garnett
Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threating diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy...
June 13, 2018: International Journal of Pharmaceutics
Pierce Radecki, Mirko Ledda, Sharon Aviran
High-throughput structure profiling (SP) experiments that provide information at nucleotide resolution are revolutionizing our ability to study RNA structures. Of particular interest are RNA elements whose underlying structures are necessary for their biological functions. We previously introduced patteRNA , an algorithm for rapidly mining SP data for patterns characteristic of such motifs. This work provided a proof-of-concept for the detection of motifs and the capability of distinguishing structures displaying pronounced conformational changes...
June 14, 2018: Genes
Duane P Grandgenett, Hideki Aihara
Integration of the reverse-transcribed viral cDNA into the host's genome is a critical step in the lifecycle of all retroviruses. Retrovirus integration is carried out by integrase (IN), a virus-encoded enzyme that forms an oligomeric 'intasome' complex with both ends of the linear viral DNA to catalyze their concerted insertions into the backbones of the host's DNA. IN also forms a complex with host proteins, which guides the intasome to the host's chromosome. Recent structural studies have revealed remarkable diversity as well as conserved features among the architectures of the intasome assembly from different genera of retroviruses...
2018: Sub-cellular Biochemistry
Robert Craigie
Integration of a DNA copy of the viral genome into host DNA is an essential step in the replication cycle of HIV-1 and other retroviruses and is an important therapeutic target for drugs. DNA integration is catalyzed by the viral integrase protein and proceeds through a series of stable nucleoprotein complexes of integrase, viral DNA ends and target DNA. These nucleoprotein complexes are collectively called intasomes. Retroviral intasomes undergo a series of transitions between initial formation and catalysis of the DNA cutting and joining steps of DNA integration...
2018: Sub-cellular Biochemistry
Liang Ma, Ousmane H Cissé, Joseph A Kovacs
Pneumocystis , a unique atypical fungus with an elusive lifestyle, has had an important medical history. It came to prominence as an opportunistic pathogen that not only can cause life-threatening pneumonia in patients with HIV infection and other immunodeficiencies but also can colonize the lungs of healthy individuals from a very early age. The genus Pneumocystis includes a group of closely related but heterogeneous organisms that have a worldwide distribution, have been detected in multiple mammalian species, are highly host species specific, inhabit the lungs almost exclusively, and have never convincingly been cultured in vitro , making Pneumocystis a fascinating but difficult-to-study organism...
July 2018: Clinical Microbiology Reviews
Bianca Cristina Leires Marques, Mariza Gonçalves Morgado, Monick Lindenmeyer Guimarães
In Brazil, detection of the HIV-1 sub-subtype F1 has decreased with a simultaneous increase in detection of the recombinant FB and FC forms. In previous HIV-1 env molecular epidemiology studies in Rio de Janeiro, 11.4% of the detected sequences were of the F1 sub-subtype. With the goal of re-estimating the prevalence of the HIV-1 F1 sub-subtype, we performed extended analyses of these samples by examining five genomic regions, resulting in 3.3% being confirmed as F1. Moreover, genomic analysis of 11 of the 21 samples identified as F1 confirmed that nine were F1 and two were BF1...
June 11, 2018: Memórias do Instituto Oswaldo Cruz
Susanna K P Lau, George C S Lo, Franklin W N Chow, Rachel Y Y Fan, James J Cai, Kwok-Yung Yuen, Patrick C Y Woo
Talaromyces marneffei is the most important thermal dimorphic fungus causing systemic mycosis in Southeast Asia. We report the discovery of a novel partitivirus, Talaromyces marneffei partitivirus -1 (TmPV1). TmPV1 was detected in 7 (12.7%) of 55 clinical T. marneffei isolates. Complete genome sequencing of the seven TmPV1 isolates revealed two double-stranded RNA (dsRNA) segments encoding RNA-dependent RNA polymerase (RdRp) and capsid protein, respectively. Phylogenetic analysis showed that TmPV1 occupied a distinct clade among the members of the genus Gammapartitivirus Transmission electron microscopy confirmed the presence of isometric, nonenveloped viral particles of 30 to 45 nm in diameter, compatible with partitiviruses, in TmPV1-infected T...
June 12, 2018: MBio
Xin-Hong Dong, Meng-Hsuan Ho, Bindong Liu, James Hildreth, Chandravanu Dash, J Shawn Goodwin, Muthukumar Balasubramaniam, Chin-Ho Chen, Hua Xie
The association between mucosal microbiota and HIV-1 infection has garnered great attention in the field of HIV-1 research. Previously, we reported a receptor-independent HIV-1 entry into epithelial cells mediated by a Gram-negative invasive bacterium, Porphyromonas gingivalis. Here, we present evidence showing that P. gingivalis outer membrane vesicles (OMVs) promote mucosal transmission of HIV-1. We demonstrated, using the Dynabeads technology, a specific interaction between HIV-1 and P. gingivalis OMVs which led to an OMV-dependent viral entry into oral epithelial cells...
June 11, 2018: Scientific Reports
Carl D Langefeld, Mary E Comeau, Maggie C Y Ng, Meijian Guan, Latchezar Dimitrov, Poorva Mudgal, Mitzie H Spainhour, Bruce A Julian, Jeffrey C Edberg, Jennifer A Croker, Jasmin Divers, Pamela J Hicks, Donald W Bowden, Gary C Chan, Lijun Ma, Nicholette D Palmer, Robert P Kimberly, Barry I Freedman
African Americans carrying two apolipoprotein L1 gene (APOL1) renal risk variants have a high risk for nephropathy. However, only a minority develops end-stage renal disease (ESRD). Hence, modifying factors likely contribute to initiation of kidney disease such as endogenous (HIV infection) or exogenous (interferon treatment) environmental modifiers. In this report, genome-wide association studies and a meta-analysis were performed to identify novel loci for nondiabetic ESRD in African Americans and to detect genetic modifiers in APOL1-associated nephropathy...
June 6, 2018: Kidney International
Rkia Eddabra, Hassan Ait Benhassou
Tuberculosis (TB) is an infectious disease that remains an important public health problem at the global level. It is one of the main causes of morbidity and mortality, due to the emergence of antibiotic resistant Mycobacterium strains and HIV co-infection. Over the past decade, important progress has been made for better control of the disease. While microscopy and culture continue to be indispensible for laboratory diagnosis of tuberculosis, the range of several molecular diagnostic tests, including the nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have expanded tremendously...
2018: Pneumonia
Chris Wymant, François Blanquart, Tanya Golubchik, Astrid Gall, Margreet Bakker, Daniela Bezemer, Nicholas J Croucher, Matthew Hall, Mariska Hillebregt, Swee Hoe Ong, Oliver Ratmann, Jan Albert, Norbert Bannert, Jacques Fellay, Katrien Fransen, Annabelle 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, Ben Berkhout, Marion Cornelissen, Paul Kellam, Peter Reiss, Christophe Fraser
Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large between- and within-host diversity, including frequent indels, may have presented a barrier...
January 2018: Virus Evolution
Maria Nevot, Ana Jordan-Paiz, Glòria Martrus, Cristina Andrés, Damir García-Cehic, Josep Gregori, Sandra Franco, Josep Quer, Miguel Angel Martinez
One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair re-engineered protease sequence including 38 (13%) synonymous mutations. WT and MAX viruses showed indistinguishable replication in MT-4 cells or PBMCs. Both viruses were subjected to serial passages in MT-4 cells with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV)...
June 6, 2018: Journal of Virology
Fabio E Leal, Soraya Maria Menezes, Emanuela A S Costa, Phillip M Brailey, Lucio Gama, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Tim Dierckx, Ricardo Khouri, Jurgen Vercauteren, Bernardo Galvão-Castro, Rui Andre Saraiva Raposo, Johan Van Weyenbergh
HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis...
2018: Frontiers in Microbiology
Shuai Liu, Qiankun Wang, Xiao Yu, Yilin Li, Yandan Guo, Zhepeng Liu, Fuyun Sun, Wei Hou, Chunmei Li, Li Wu, Deyin Guo, Shuliang Chen
The C-X-C chemokine receptor type 4 (CXCR4) is one of the major co-receptors for human immunodeficiency virus type 1 (HIV-1) entry and is considered an important therapeutic target. However, its function in maintaining the development of hematopoietic stem cells (HSC) makes it difficult to be used for HIV-1 gene therapy with HSC transplantation. A previous report showed that the natural CXCR4 P191A mutant inhibits HIV-1 infection without any defect in HSC differentiation, which could provide a basis for the development of new approaches for HIV-1 gene therapy...
June 5, 2018: Scientific Reports
Adrienne E Swanstrom, Robert J Gorelick, Guoxin Wu, Bonnie Howell, Anitha Vijayagopalan, Rebecca Shoemaker, Kelli Oswald, Siddhartha A Datta, Brandon Keele, Gregory Del Prete, Elena Chertova, Julian Bess, Jeffrey Lifson
Although effective at suppressing viral replication, combination antiretroviral treatment (cART) does not represent definitive therapy of HIV infection due to persistence of replication-competent viral reservoirs. The advent of effective cART regimens for simian immunodeficiency virus (SIV) infected nonhuman primates (NHP) has enabled the development of relevant models for studying viral reservoirs and intervention strategies targeting them. Viral reservoir measurements are crucial for such studies, but are problematic...
June 5, 2018: AIDS Research and Human Retroviruses
Susan Northfield, Jerome Wielens, Stephen Headey, Billy Williams-Noonan, Mark Mulcair, Martin Scanlon, Michael Parker, Philip Thompson, David Chalmers
The p75 splice variant of lens epithelium-derived growth factor (LEDGF) is a 75 kDa protein that is recruited by the human immunodeficiency virus (HIV) to tether the pre-integration complex to the host chromatin and promote integration of proviral DNA into the host genome. We have designed a series of small cyclic peptides that are structural mimics of the LEDGF binding domain, which interact with integrase as potential binding inhibitors. Here we present the X-ray crystal structures, NMR studies, SPR analysis and conformational studies of four cyclic peptides bound to the HIV-1 integrase core domain...
June 4, 2018: ChemMedChem
Bowen Wang, Jiahui Zuo, Wenzhen Kang, Qianqi Wei, Jianhui Li, Chunfu Wang, Zhihui Liu, Yuanan Lu, Yan Zhuang, Bianli Dang, Qing Liu, Wen Kang, Yongtao Sun
The ability of monocytes to travel through the bloodstream, traverse tissue barriers, and aggregate at disease sites endows these cells with the attractive potential to carry therapeutic genes into the nervous system. However, gene editing in primary human monocytes has long been a challenge. Here, we applied the CRISPR/Cas9 system to deliver the large functional Hutat2:Fc DNA fragment into the genome of primary monocytes to neutralize HIV-1 transactivator of transcription (Tat), an essential neurotoxic factor that causes HIV-associated neurocognitive disorder (HAND) in the nervous system...
June 1, 2018: Molecular Therapy. Nucleic Acids
Heng-Chang Chen, Eduard Zorita, Guillaume J Filion
The latent HIV reservoir is the main barrier to curing AIDS, because infected cells escape the immune system and antiretroviral therapies. Developing new treatment strategies requires technologies to trace latent proviruses. Here, we describe a genome-wide technique called Barcoded HIV Ensembles (B-HIVE) to measure HIV expression at the single provirus level. The principle of B-HIVE is to tag the genome of HIV with DNA barcodes to trace viral transcripts produced by single proviruses in an infected cell population...
April 2018: Current Protocols in Molecular Biology
Gatikrushna Singh, Brittany D Rife, Bradley Seufzer, Marco Salemi, Aaron Rendahl, Kathleen Boris-Lawrie
Precise stoichiometry of genome-length transcripts and alternatively spliced mRNAs is a hallmark of retroviruses. We discovered short, guanosine and adenosine sequence motifs in the 5'untranslated region of several retroviruses and ascertained the reasons for their conservation using a representative lentivirus and genetically simpler retrovirus. We conducted site-directed mutagenesis of the GA-motifs in HIV molecular clones and observed steep replication delays in T-cells. Quantitative RNA analyses demonstrate the GA-motifs are necessary to retain unspliced viral transcripts from alternative splicing...
May 26, 2018: Nucleic Acids Research
Isabelle Malet, Frédéric Subra, Clémence Richetta, Charlotte Charpentier, Gilles Collin, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
No abstract text is available yet for this article.
May 29, 2018: MBio
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