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HIV viral dynamics

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https://www.readbyqxmd.com/read/28431573/a-highly-pathogenic-simian-human-immunodeficiency-virus-effectively-produces-infectious-virions-compared-with-a-less-pathogenic-virus-in-cell-culture
#1
Shoya Iwanami, Yusuke Kakizoe, Satoru Morita, Tomoyuki Miura, Shinji Nakaoka, Shingo Iwami
BACKGROUND: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments...
April 21, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28423342/a-broadly-neutralizing-antibody-targets-the-dynamic-hiv-envelope-trimer-apex-via-a-long-rigidified-and-anionic-%C3%AE-hairpin-structure
#2
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A Cottrell, Travis Nieusma, Claudia Blattner, James C Paulson, Per Johan Klasse, Ian A Wilson, Dennis R Burton, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422752/t-bet-b-cells-are-induced-by-human-viral-infections-and-dominate-the-hiv-gp140-response
#3
James J Knox, Marcus Buggert, Lela Kardava, Kelly E Seaton, Michael A Eller, David H Canaday, Merlin L Robb, Mario A Ostrowski, Steven G Deeks, Mark K Slifka, Georgia D Tomaras, Susan Moir, M Anthony Moody, Michael R Betts
Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28416550/identification-and-optimization-of-thienopyridine-carboxamides-as-inhibitors-of-hiv-regulatory-complexes
#4
Robert L Nakamura, Mark A Burlingame, Shumin Yang, David C Crosby, Dale J Talbot, Kitty Chui, Alan D Frankel, Adam R Renslo
Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many proteins and are dynamic, making them difficult to fully recapitulate in vitro Therefore we developed a cell-based reporter assay to monitor the assembly of viral complexes for inhibitor screening. We screened a small molecule library and identified multiple hits that inhibit the activity of the viral complexes...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28411091/comparison-of-dynamic-monitoring-strategies-based-on-cd4-cell-counts-in-virally-suppressed-hiv-positive-individuals-on-combination-antiretroviral-therapy-in-high-income-countries-a-prospective-observational-study
#5
Ellen C Caniglia, Lauren E Cain, Caroline A Sabin, James M Robins, Roger Logan, Sophie Abgrall, Michael J Mugavero, Sonia Hernández-Díaz, Laurence Meyer, Remonie Seng, Daniel R Drozd, George R Seage, Fabrice Bonnet, Francois Dabis, Richard D Moore, Peter Reiss, Ard van Sighem, William C Mathews, Julia Del Amo, Santiago Moreno, Steven G Deeks, Roberto Muga, Stephen L Boswell, Elena Ferrer, Joseph J Eron, Sonia Napravnik, Sophie Jose, Andrew Phillips, Amy C Justice, Janet P Tate, John Gill, Antonio Pacheco, Valdilea G Veloso, Heiner C Bucher, Matthias Egger, Hansjakob Furrer, Kholoud Porter, Giota Touloumi, Heidi Crane, Jose M Miro, Jonathan A Sterne, Dominique Costagliola, Michael Saag, Miguel A Hernán
BACKGROUND: Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. METHODS: In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems...
April 11, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#6
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28401776/molecular-characteristics-of-the-envelope-of-vertically-transmitted-hiv-1-strains-from-infants-with-hiv-infection
#7
Manickam Ashokkumar, Manohar Nesakumar, Cheedarla Narayanaiah, Vidya Vijayan Kk, Babu Hemalatha, Srikanth P Tripathy, Luke Elizabeth Hanna
Mother-to-child transmission of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV infected infants (< 2 years)...
April 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28392419/early-phase-dynamics-of-traceable-mcherry-fluorescent-protein-carrying-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells-transplanted-nod-scid-jak3-mice
#8
Nobuyo Higashi-Kuwata, Hiromi Ogata-Aoki, Shin-Ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Tatsuyoshi Kawamura, Hironobu Ihn, Hisataka Kobayashi, Seiji Okada, Hiroaki Mitsuya
We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FL(mC)) and NOD/SCID/Jak3(-/-) mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FL(mC) inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FL(mC)-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6)...
April 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28381571/discovery-of-novel-small-molecule-inhibitors-of-lim-domain-kinase-for-inhibiting-hiv-1
#9
Fei Yi, Jia Guo, Deemah Dabbagh, Mark Spear, Sijia He, Kylene Kehn-Hall, Jacque Fontenot, Yan Yin, Mathieu Bibian, Chul Min Park, Ke Zheng, HaJeung Park, Veronica Soloveva, Dima Gharaibeh, Cary Retterer, Rouzbeh Zamani, Margaret L Pitt, John Naughton, Yongjun Jiang, Hong Shang, Ramin M Hakami, Binhua Ling, John A T Young, Sina Bavari, Xuehua Xu, Yangbo Feng, Yuntao Wu
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling which activates a host dependency factor cofilin and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIMK1 with shRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK was available. Here we describe the design and discovery of novel classes of small molecule inhibitors of LIMK for inhibiting HIV infection...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28380038/impact-of-cd4-and-cd8-dynamics-and-viral-rebounds-on-loss-of-virological-control-in-hiv-controllers
#10
Fanny Chereau, Yoann Madec, Caroline Sabin, Niels Obel, Ezequiel Ruiz-Mateos, Georgios Chrysos, Sarah Fidler, Clara Lehmann, Robert Zangerle, Linda Wittkop, Peter Reiss, Osamah Hamouda, Vicente Estrada Perez, Manuel Leal, Amanda Mocroft, Patricia Garcia De Olalla, Adriana Ammassari, Antonella D'Arminio Monforte, Cristina Mussini, Ferran Segura, Antonella Castagna, Matthias Cavassini, Sophie Grabar, Philippe Morlat, Stéphane De Wit, Olivier Lambotte, Laurence Meyer
OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. METHODS: HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis...
2017: PloS One
https://www.readbyqxmd.com/read/28371581/single-particle-tracking-of-human-immunodeficiency-virus-type-1-productive-entry-into-human-primary-macrophages
#11
Qin Li, Wei Li, Wen Yin, Jia Guo, Zhi-Ping Zhang, Dejun Zeng, Xiaowei Zhang, Yuntao Wu, Xian-En Zhang, Zongqiang Cui
Macrophages are one of the major targets of human immunodeficiency virus (HIV-1), but the viral entry pathway remains poorly understood in these cells. Noninvasive virus labeling and single-virus tracking are effective tools for studying virus entry. Here, we constructed a quantum dot (QD)-encapsulated infectious HIV-1 particle to track viral entry at a single-particle level in live human primary macrophages. QDs were encapsulated in HIV-1 virions by incorporating viral accessory protein Vpr-conjugated QDs during virus assembly...
April 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28362805/effects-of-contact-structure-on-the-transient-evolution-of-hiv-virulence
#12
Sang Woo Park, Benjamin M Bolker
Early in an epidemic, high densities of susceptible hosts select for relatively high parasite virulence; later in the epidemic, lower susceptible densities select for lower virulence. Thus over the course of a typical epidemic the average virulence of parasite strains increases initially, peaks partway through the epidemic, then declines again. However, precise quantitative outcomes, such as the peak virulence reached and its timing, may depend sensitively on epidemiological details. Fraser et al. proposed a model for the eco-evolutionary dynamics of HIV that incorporates the tradeoffs between transmission and virulence (mediated by set-point viral load, SPVL) and their heritability between hosts...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28348854/bayesian-codon-substitution-modelling-to-identify-sources-of-pathogen-evolutionary-rate-variation
#13
Guy Baele, Marc A Suchard, Filip Bielejec, Philippe Lemey
Phylodynamic reconstructions rely on a measurable molecular footprint of epidemic processes in pathogen genomes. Identifying the factors that govern the tempo and mode by which these processes leave a footprint in pathogen genomes represents an important goal towards understanding infectious disease evolution. Discriminating between synonymous and non-synonymous substitution rates is crucial for testing hypotheses about the sources of evolutionary rate variation. Here, we implement a codon substitution model in a Bayesian statistical framework to estimate absolute rates of synonymous and non-synonymous substitution in unknown evolutionary histories...
June 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28341641/proliferation-of-latently-infected-cd4-t-cells-carrying-replication-competent-hiv-1-potential-role-in-latent-reservoir-dynamics
#14
Nina N Hosmane, Kyungyoon J Kwon, Katherine M Bruner, Adam A Capoferri, Subul Beg, Daniel I S Rosenbloom, Brandon F Keele, Ya-Chi Ho, Janet D Siliciano, Robert F Siliciano
A latent reservoir for HIV-1 in resting CD4(+) T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28338097/the-cellular-protein-hnrnp-a2-b1-enhances-hiv-1-transcription-by-unfolding-ltr-promoter-g-quadruplexes
#15
Matteo Scalabrin, Ilaria Frasson, Emanuela Ruggiero, Rosalba Perrone, Elena Tosoni, Sara Lago, Martina Tassinari, Giorgio Palù, Sara N Richter
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315414/the-dynamics-of-hcv-specific-antibody-responses-in-hiv-hcv-patients-on-long-term-antiretroviral-therapy
#16
Silvia Lee, Alfred Laiman, Martyn A French, James Flexman, Mark W Watson, Patricia Price
Antibody responses have not been fully characterised in chronically HIV/HCV patients receiving antiretroviral therapy (ART). Seventeen HIV/HCV patients receiving ART were followed for a median (range) interval of 597 (186-766) weeks. Prior to ART, HIV/HCV patients had lower levels of antibodies reactive with HCV core and JFH-1, and lower genotype cross-reactive neutralising antibodies (nAb) titres, than HCV patients. Levels of JFH-1 reactive antibody increased on ART, irrespective of CD4(+) T-cell counts or changes in serum ALT levels...
March 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28296911/longitudinal-dynamics-of-the-hiv-specific-b-cell-response-during-intermittent-treatment-of-primary-hiv-infection
#17
Godelieve J de Bree, Adam K Wheatley, Rebecca M Lynch, Madhu Prabhakaran, Marlous L Grijsen, Jan M Prins, Stephen D Schmidt, Richard A Koup, John R Mascola, Adrian B McDermott
BACKGROUND: Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28295345/the-viral-protein-gp120-decreases-the-acetylation-of-neuronal-tubulin-potential-mechanism-of-neurotoxicity
#18
Valeria Avdoshina, Seamus P Caragher, Erin D Wenzel, Francesca Taraballi, Italo Mocchetti, G Jean Harry
The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV-mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post-translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules...
March 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28251415/a-molecular-dynamics-simulation-study-decodes-the-early-stage-of-the-disassembly-process-abolishing-the-human-samhd1-function
#19
Francesca Cardamone, Federico Iacovelli, Giovanni Chillemi, Mattia Falconi, Alessandro Desideri
The human sterile alpha motif SAM and HD domain-containing protein 1 (SAMHD1) restricts in non-cycling cells type the infection of a large range of retroviruses including HIV-1, reducing the intracellular pool concentration of deoxynucleoside triphosphates (dNTPs) required for the reverse transcription of the viral genome. The enzyme is in equilibrium between different forms depending on bound cofactors and substrate. In this work, two SAMHD1 three-dimensional models have been investigated through classical molecular dynamics simulation, to define the role of cofactors and metal ions in the association of the tetrameric active form...
March 1, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28250813/modelling-the-evolution-of-hiv-1-virulence-in-response-to-imperfect-therapy-and-prophylaxis
#20
David R M Smith, Nicole Mideo
Average HIV-1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to "leaky" therapy (treatment that imperfectly suppresses viral replication) and the use of preventive drugs (pre-exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is imperfectly effective and that this evolution erodes some of the long-term clinical and epidemiological benefits of HIV treatment...
March 2017: Evolutionary Applications
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