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HIV genomics

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https://www.readbyqxmd.com/read/28542550/a-spatio-temporal-assessment-of-simian-human-immunodeficiency-virus-shiv-evolution-reveals-a-highly-dynamic-process-within-the-host
#1
Alison F Feder, Christopher Kline, Patricia Polacino, Mackenzie Cottrell, Angela D M Kashuba, Brandon F Keele, Shiu-Lok Hu, Dmitri A Petrov, Pleuni S Pennings, Zandrea Ambrose
The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points. To directly measure how drug resistance spreads within a host and to assess how spatial structure impacts its emergence, we examined serial sequences from four macaques infected with RT-SHIVmne027, a simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT), and treated with RT inhibitors...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#2
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28540745/uvaria-angolensis-as-a-promising-source-of-inhibitors-of-hiv-1-rt-associated-rna-dependent-dna-polymerase-and-rnase-h-functions
#3
Alvine Ngoutane Mfopa, Angela Corona, Kodjo Eloh, Enzo Tramontano, Aldo Frau, Fabrice Fekam Boyom, Pierluigi Caboni, Graziella Tocco
Reverse transcriptase (RT)-associated DNA polymerase (RDDP) and ribonucleaser H (RNase H) functions are both essential for HIV-1 genome replication, and the identification of new inhibitors to block both of them is a goal actively pursued by the scientific community. In this field, natural extracts have shown a great potential as source of new antivirals. In the present work, we investigated the effect of Uvaria angolensis extracts on the HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities...
May 25, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28539453/epigenetic-metabolite-acetate-inhibits-class-i-ii-histone-deacetylases-promotes-histone-acetylation-and-increases-hiv-1-integration-in-cd4-t-cells
#4
Jean-François Bolduc, Laurent Hany, Corinne Barat, Michel Ouellet, Michel J Tremblay
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539452/interactions-between-hiv-1-gag-and-viral-rna-genome-enhance-virion-assembly
#5
Kari A Dilley, Olga A Nikolaitchik, Andrea Galli, Ryan C Burdick, Louis Levine, Kelvin Li, Alan Rein, Vinay K Pathak, Wei-Shau Hu
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536474/gcn2-phosphorylates-hiv-1-integrase-and-decreases-hiv-1-replication-by-limiting-viral-integration
#6
A Jaspart, C Calmels, O Cosnefroy, P Bellecave, P Pinson, S Claverol, V Guyonnet-Dupérat, B Dartigues, M S Benleulmi, E Mauro, P A Gretteau, V Parissi, M Métifiot, M L Andreola
GCN2 is a serine/threonine kinase involved in cellular stress response related to amino acid starvation. Previously, we showed that GCN2 interacts with HIV-1 integrase and is activated during HIV-1 infection. Herein, we identified HIV-1 integrase as a previously unknown substrate of GCN2 in vitro with a major site of phosphorylation at residue S255 located in the C-terminal domain of HIV-1 integrase. The underlying mechanism was investigated and it appeared that the integrase active site was required in order for GCN2 to target the integrase residue S255...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535668/stability-of-retroviral-vectors-against-ultracentrifugation-is-determined-by-the-viral-internal-core-and-envelope-proteins-used-for-pseudotyping
#7
Soo-Hyun Kim, Kwang-Il Lim
Retroviral and lentiviral vectors are mostly pseudotyped and often purified and concentrated via ultracentrifugation. In this study, we quantified and compared the stabilities of retroviral [murine leukemia virus (MLV)-based] and lentiviral [human immunodeficiency virus (HIV)-1-based] vectors pseudotyped with relatively mechanically stable envelope proteins, vesicular stomatitis virus glycoproteins (VSVGs), and the influenza virus WSN strain envelope proteins against ultracentrifugation. Lentiviral genomic and functional particles were more stable than the corresponding retroviral particles against ultracentrifugation when pseudotyped with VSVGs...
May 2, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28529033/high-throughput-characterization-of-hiv-1-reservoir-reactivation-using-a-single-cell-in-droplet-pcr-assay
#8
Robert W Yucha, Kristen S Hobbs, Emily Hanhauser, Louise E Hogan, Wildaliz Nieves, Mehmet O Ozen, Fatih Inci, Vanessa York, Erica A Gibson, Cassandra Thanh, Hadi Shafiee, Rami El Assal, Maja Kiselinova, Yvonne P Robles, Helen Bae, Kaitlyn S Leadabrand, ShuQi Wang, Steven G Deeks, Daniel R Kuritzkes, Utkan Demirci, Timothy J Henrich
Reactivation of latent viral reservoirs is on the forefront of HIV-1 eradication research. However, it is unknown if latency reversing agents (LRAs) increase the level of viral transcription from cells producing HIV RNA or harboring transcriptionally-inactive (latent) infection. We therefore developed a microfluidic single-cell-in-droplet (scd)PCR assay to directly measure the number of CD4(+) T cells that produce unspliced (us)RNA and multiply spliced (ms)RNA following ex vivo latency reversal with either an histone deacetylase inhibitor (romidepsin) or T cell receptor (TCR) stimulation...
May 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28520964/proviral-latency-persistent-human-immunodeficiency-virus-infection-and-the-development-of-latency-reversing-agents
#9
David M Margolis, Nancie M Archin
Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520963/humoral-and-innate-antiviral-immunity-as-tools-to-clear-persistent-hiv-infection
#10
Guido Ferrari, Justin Pollara, Georgia D Tomaras, Barton F Haynes
Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28513417/carriage-of-extended-spectrum-beta-lactamase-producing-enterobacteriaceae-in-hiv-infected-children-in-zimbabwe
#11
S M S Wilmore, K Kranzer, A Williams, B Makamure, A F Nhidza, J Mayini, T Bandason, J Metcalfe, M P Nicol, I Balakrishnan, M J Ellington, N Woodford, S Hopkins, T D McHugh, R A Ferrand
BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28511559/migrating-microbes-what-pathogens-can-tell-us-about-population-movements-and-human-evolution
#12
Charlotte J Houldcroft, Jean-Baptiste Ramond, Riaan F Rifkin, Simon J Underdown
BACKGROUND: The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases...
May 16, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28509569/hiv-1-crf07_bc-with-a-seven-amino-acid-deletion-in-the-gag-p6-region-dominates-in-hiv-1-infected-men-who-have-sex-with-men-in-china
#13
Yue Wu, Haiying Wang, Xuqi Ren, Zhengwei Wan, Guifang Hu, Shixing Tang
We examined sequence variation in the HIV-1 gag p6 region from 27 individuals infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from the Los Alamos National Laboratory database were also analyzed. A unique deletion of seven amino acid (aa) (p6Δ7) (aa 30-36, PIDKELY, in the HXB2 genome) was observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the CRF07_BC sequences contained the p6Δ7 mutation. The prevalence of the p6Δ7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected intravenous drug users and men who have sex with men (MSM), respectively...
May 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28508728/high-frequency-of-identical-clonal-immunoglobulin-dna-in-pre-treatment-tumor-and-plasma-from-untreated-patients-with-hiv-associated-lymphoma-prospective-multicenter-trial-of-the-aids-malignancies-consortium-amc-064
#14
Nina D Wagner-Johnston, Shelly Lensing, Ariela Noy, Lee Ratner, David Henry, Jeannette Y Lee, Sylvia Silver, Malek Faham, Richard F Ambinder
Patients with HIV are at increased risk for developing B-cell lymphomas likely due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig) gene rearrangements. Next-generation sequencing (NGS)-based identification of circulating Ig clonotypes has not been well-characterized in HIV-related lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for Ig clonotypes using an NGS approach (AMC064, NCT00981097)...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28507544/within-epitope-interactions-can-bias-ctl-escape-estimation-in-early-hiv-infection
#15
Victor Garcia, Marcus W Feldman
As human immunodeficiency virus (HIV) begins to replicate within hosts, immune responses are elicited against it. Escape mutations in viral epitopes-immunogenic peptide parts presented on the surface of infected cells-allow HIV to partially evade these responses, and thus rapidly go to fixation. The faster they go to fixation, i.e., the higher their escape rate, the larger the selective pressure exerted by the immune system is assumed to be. This relation underpins the rationale for using escapes to assess the strength of immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28505234/increased-risk-for-meningococcal-disease-among-men-who-have-sex-with-men-in-the-united-states-2012-2015
#16
Temitope A Folaranmi, Cecilia B Kretz, Hajime Kamiya, Jessica R MacNeil, Melissa J Whaley, Amy Blain, Mike Antwi, Marie Dorsinville, Massimo Pacilli, Shamika Smith, Rachel Civen, Van Ngo, Kathleen Winter, Kathleen Harriman, Xin Wang, Virginia B Bowen, Manisha Patel, Stacey Martin, Lara Misegades, Sarah A Meyer
Background: Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well-described. Methods: All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described...
May 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28497113/toward-a-cure-does-host-immunity-play-a-role
#17
Jielin Zhang, Clyde S Crumpacker
Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal that the human body has developed through evolution a genome immune system embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV infection, this epigenetic regulation plays a cardinal role in HIV RNA production that silences HIV transcription at a molecular (RNA) level, controls viral load at a cellular (biological) level, and governs the viremic stage of AIDS at the clinical (patient) level. Even though the human genome is largely similar among humans and HIV is a single viral species, human hosts show significant differences in viral RNA levels, ranging from cell to organ to individual and expressed as elite controllers, posttreatment controllers, and patients with AIDS...
March 2017: MSphere
https://www.readbyqxmd.com/read/28490747/structural-basis-for-importin-%C3%AE-binding-of-the-human-immunodeficiency-virus-tat
#18
K M Smith, Z Himiari, S Tsimbalyuk, J K Forwood
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484438/the-role-of-hcmv-and-hiv-1-micrornas-processing-and-mechanisms-of-action-during-viral-infection
#19
REVIEW
Doriana Fruci, Rossella Rota, Angela Gallo
Viruses infect host cells releasing their genome (DNA or RNA) containing all information needed to replicate themselves. The viral genome takes control of the cells and helps the virus to evade the host immune system. Some viruses alter the functions of infected cells without killing them. In some cases infected cells lose control over normal cell proliferation and becomes cancerous. Viruses, such as HCMV and HIV-1, may leave their viral genome in the host cells for a certain period (latency) and begin to replicate when the cells are stressed causing diseases...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28481902/association-of-hiv-diversity-and-virologic-outcomes-in-early-antiretroviral-treatment-hptn-052
#20
Philip J Palumbo, Ethan A Wilson, Estelle Piwowar-Manning, Marybeth McCauley, Theresa Gamble, Newton Kumwenda, Joseph Makhema, Nagalingeswaran Kumarasamy, Suwat Chariyalertsak, James G Hakim, Mina C Hosseinipour, Marineide G Melo, Sheela V Godbole, Jose H Pilotto, Beatriz Grinsztejn, Ravindre Panchia, Ying Q Chen, Myron S Cohen, Susan H Eshleman, Jessica M Fogel
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure...
2017: PloS One
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