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HIV genomics

Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I Bukrinsky, Paul J Brindley
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein...
October 2016: PLoS Pathogens
K V Shur, M V Zaychikova, N E Mikheecheva, K M Klimina, O B Bekker, S N Zhdanova, O B Ogarkov, V N Danilenko
We report a draft genome sequence of Mycobacterium tuberculosis strain B9741 belonging to Beijing B0/W lineage isolated from a HIV patient from Siberia, Russia. This clinical isolate showed MDR phenotype and resistance to isoniazid, rifampin, streptomycin and pyrazinamide. We analyzed SNPs associated with virulence and resistance. The draft genome sequence and annotation have been deposited at GenBank under the accession NZ_LVJJ00000000.
December 2016: Genomics Data
Julie Yamaguchi, Catherine A Brennan, Elodie Alessandri, Jean-Christophe Plantier, Gavin Cloherty, Michael G Berg
HIV-2 exhibits a natural history of infection distinct from HIV-1. Primarily found in West Africa and in only 10-20% of HIV infections in this region, patients with HIV-2 typically exhibit a slower progression to AIDS, lower viral loads, and decreased rates of transmission. Here we used next-generation sequencing (NGS) to determine the sequence and phylogenetic classification of 9 HIV-2 genomes. We identified a patient with a series of mutations in an invariant cytotoxic lymphocyte (CTL)-restricted gag epitope required for retroviral structure and replication, and implicated in long-term non-progression to AIDS...
October 19, 2016: AIDS Research and Human Retroviruses
T Hertz, M G Logan, M Rolland, C A Magaret, C Rademeyer, A Fiore-Gartland, P T Edlefsen, A DeCamp, H Ahmed, N Ngandu, B B Larsen, N Frahm, J Marais, R Thebus, D Geraghty, J Hural, L Corey, J Kublin, G Gray, M J McElrath, J I Mullins, P B Gilbert, C Williamson
INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients...
October 15, 2016: Vaccine
Denis R Chopera, Roman Ntale, Nonkululeko Ndabambi, Nigel Garrett, Clive M Gray, David Matten, Quarraisha Abdool Karim, Salim Abdool Karim, Carolyn Williamson
OBJECTIVE: HIV-1 escape from cytotoxic T-lymphocytes (CTL) results in the accumulation of HLA-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of CTL escape in a cohort followed from infection for five years. METHODS: Viral loads and CD4+ counts were monitored in 78 subtype C infected individuals from onset of infection until CD4+ decline to <350 cells/μl or five years post-infection...
October 14, 2016: AIDS
Qian Wang, Renato Polimanti, Henry R Kranzler, Lindsay A Farrer, Hongyu Zhao, Joel Gelernter
Schizophrenia (SZ) and HIV infection are serious disorders with a complex phenotypic relationship. Observational studies have described their comorbidity; their genetic correlation is not well studied. We performed extensive analysis in search of common genetic factors for SZ and HIV, and their relationship with risky sexual behavior (RSB). Summary statistics from genome-wide association studies of HIV infection and schizophrenia were obtained and 2379 European Americans were genotyped and assessed for RSB score...
October 17, 2016: Human Genetics
Jian Huang, Lei Zhao, Ping Yang, Zhen Chen, Ni Tang, Xiong Z Ruan, Yaxi Chen
Hepatitis B virus (HBV) is a hepatocyte-specific DNA virus whose gene expression and replication are closely associated with hepatic metabolic processes. Thus, a potential anti-viral strategy is to target the host metabolic factors necessary for HBV gene expression and replication. Recent studies revealed that fatty acid translocase CD36 is involved in the replication, assembly, storage, and secretion of certain viruses, such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV). However, the relationship between CD36 and the HBV life cycle remains unclear...
2016: PloS One
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Jianbin Wang, Michael C Holmes
The battle with human immunodeficiency virus (HIV) has been ongoing for more than 30 years, and although progress has been made, there are still significant challenges remaining. A few unique features render HIV to be one of the toughest viruses to conquer in the modern medicine era, such as the ability to target the host immune system, persist by integrating into the host genome and adapt to a hostile environment such as a single anti-HIV medication by continuously evolving. The finding of combination anti-retroviral therapy (cART) about 2 decades ago has transformed the treatment options for HIV-infected patients and significantly improved patient outcomes...
November 2016: Cytotherapy
Xiaotang Hu
Since 2012, the CRISPR-Cas9 system has been quickly and successfully tested in a broad range of organisms and cells including hematopoietic cells. The application of CRISPR-Cas9 in human hematopoietic cells mainly involves the genes responsible for HIV infection, β-thalassemia and sickle cell disease (SCD). The successful disruption of CCR5 and CXCR4 genes in T cells by CRISPR-Cas9 promotes the prospect of the technology in the functional cure of HIV. More recently, eliminating CCR5 and CXCR4 in induced pluripotent stem cells (iPSCs) derived from patients and targeting the HIV genome have been successfully carried out in several laboratories...
October 2, 2016: Blood Cells, Molecules & Diseases
Dan-Dan He, Yueer Lu, Rachel Gittelman, Yabin Jin, Fei Ling, Akey Joshua
Viral selection pressure has acted on restriction factors that play an important role in the innate immune system by inhibiting the replication of viruses during primate evolution. Tripartite motif-containing (TRIM) family members are some of these restriction factors. It is becoming increasingly clear that gene expression differences, rather than protein-coding regions changes, could play a vital role in the anti-retroviral immune mechanism. Increasingly, recent studies have created genome-scale catalogues of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA...
October 12, 2016: Proceedings. Biological Sciences
Sutapa Khatua, Abby M Geltemeyer, Anand Gourishankar
Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of Tuberculosis. During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing Mycobacterium Tuberculosis.TB is the second most common cause of death from infectious diseases after HIV/AIDS...
October 10, 2016: Pediatric Research
Ann Baeyens, Evelien Naessens, Anouk Van Nuffel, Karin E Weening, Anne-Marie Reilly, Eva Claeys, Wim Trypsteen, Linos Vandekerckhove, Sven Eyckerman, Kris Gevaert, Bruno Verhasselt
To facilitate studies on Vpr function in replicating HIV-1, we aimed to tag the protein in an infectious virus. First we showed that N-, but not C-terminal HA/FLAG tagging of Vpr protein preserves Vpr cytopathicity. Cloning the tags into proviral DNA however ablated viral production and replication. By construction of additional viral variants we could show this defect was not protein- but RNA-dependent and sequence specific, and characterized by oversplicing of the genomic RNA. Simulation of genomic RNA folding suggested that introduction of the tag sequence induced an alternative folding structure in a region enriched in splice sites and splicing regulatory sequences...
October 10, 2016: Scientific Reports
Diana M Giraldo, Juan C Hernandez, Silvio Urcuqui-Inchima
Neutrophils are key effector cells of the innate immune system and are involved in the host defense against invading pathogens such as viruses. Recently, it was reported that HIV-1-neutrophil interaction triggers neutrophil activation and promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We observed functional activation of neutrophils in response to HIV-1-derived ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of cytokines (IL-6 and TNF-α), and the production of reactive oxygen species (ROS)...
October 7, 2016: Immunologic Research
Ashley Azar, Kathryn Devlin, Joshua Chang Mell, Tania Giovannetti, Vanessa Pirrone, Michael R Nonnemacher, Shendra Passic, Katherine Kercher, Jean W Williams, Jeffery M Jacobson, Brian Wigdahl, William Dampier, David J Libon, Christian Sell
Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes...
2016: PloS One
Giórgia de Souza Marasca, André Luiz Machado, Nélson Alexandre Kretzmann, Adaliany Cecília da Silva Souza, Angelo Alves de Mattos, Dimas Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini da Veiga
Background: Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients...
October 2016: Arquivos de Gastroenterologia
Ronald Moura Rodrigues, Monserrat Plana, Felipe Garcia, Luisa Zupin, Louise Kuhn, Sergio Crovella
We performed a retrospective genome-wide association study in HIV-infected individuals who were treated with dendritic cell-based immunotherapy in clinical trials performed by two research groups (Spain and Brazil). We aimed to identify host genetic variants influencing treatment response. The Illumina Human Core Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic factors affecting treatment response. Additionally, we performed a meta-analysis of the results obtained from Spanish and Brazilian patients...
October 4, 2016: Immunologic Research
Yingxin Ma, Zongqiang Cui, Zhike He, Wei Li, Zhi-Ping Zhang, Xiaowei Zhang, Xian-En Zhang, Tianwei Tan
Photobleaching is a major obstacle in the real-time imaging of biological events, particularly at the single-molecule/particle level. Here, we report a strategy to delay photobleaching of a light-switch complex, [Ru(phen)2dppx]2+, by insertion of a six-cysteine peptide into virus particles. The six-cysteine peptide was inserted into viral protein R of HIV-1, and assembled into infectious HIV-1 viral particles, where it effectively delayed the photobleaching of the [Ru(phen)2dppx]2+ complex used to label viral genomic RNAs...
October 4, 2016: Analytical Chemistry
Nirajan Bhusal, Ruengpung Sutthent, Navin Horthongkham, Niracha Athipanyasilp, Wannee Kantakamalakul
BACKGROUND: There have been very few reports of HIV-1 subtypes and drug resistance mutations (DRMs) from Nepal which is geographically located between two high-prevalence HIV-1 infection countries, China and India. The aim of this study was to determine prevalence of acquired and transmitted DRMs and HIV-1 subtypes in Nepal. METHODS: Thirty-five HIV-1 seropositive samples from central region of Nepal were collected in 2011. The subjects were divided into two groups, antiretroviral (ARV) drug naïve group (n=15) and antiretroviral treatment (ART) group (n=20), 90% (18/20) of them received zidovudine, lamivudine and nevirapine (AZT/3TC/NVP) regimen...
October 3, 2016: Current HIV Research
Mette T Christiansen, Sebastiaan J Hullegie, Martin Schutten, Katja Einer-Jensen, Helena J Tutill, Judith Breuer, Bart J A Rijnders
OBJECTIVES: ; Within HIV positive men having sex with men the epidemic of hepatitis C (HCV) is ongoing. Transmission of resistant variants of HCV after failure of treatment with directly acting antivirals (DAA) could be a major threat to the effectivity of therapy. We determined whether HCV resistant variants to DAAs were prevalent amongst patients with an acute HCV infection diagnosed in 2013 and 2014 in the Netherlands. METHODS: Target enrichment for viral nucleic acid separation and deep sequencing were used to recover whole HCV genomes of 50 patients with an acute HCV infection...
September 28, 2016: Clinical Microbiology and Infection
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