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HIV viral dynamics

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https://www.readbyqxmd.com/read/28100241/personalized-life-expectancy-and-treatment-benefit-index-of-antiretroviral-therapy
#1
Yanni Xiao, Xiaodan Sun, Sanyi Tang, Yicang Zhou, Zhihang Peng, Jianhong Wu, Ning Wang
BACKGROUND: The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART. METHODS: We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function...
January 18, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28095513/changes-in-circulating-b-cell-subsets-associated-with-aging-and-acute-siv-infection-in-rhesus-macaques
#2
W L William Chang, Denise F Gonzalez, Hung T Kieu, Luis D Castillo, Ilhem Messaoudi, Xiaoying Shen, Georgia D Tomaras, Barbara L Shacklett, Peter A Barry, Ellen E Sparger
Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques...
2017: PloS One
https://www.readbyqxmd.com/read/28077634/characterization-of-hcv-envelope-diversification-from-acute-to-chronic-infection-using-smrt-sequencing-within-a-sexually-transmitted-hepatitis-c-virus-cluster
#3
Cynthia K Y Ho, Jayna Raghwani, Sylvie Koekkoek, Richard H Liang, Jan T M Van der Meer, Marc Van Der Valk, Menno De Jong, Oliver G Pybus, Janke Schinkel, Richard Molenkamp
: In contrast to other available next generation sequencing platforms, Pacbio Single Molecule, Real-Time (SMRT) sequencing has the advantage of generating long reads, albeit with a relatively higher error rate in unprocessed data. Using this platform we longitudinally sampled and sequenced the hepatitis C virus (HCV) envelope genome region (1680 nt) from individuals belonging to a cluster of sexually-transmitted cases. All five subjects were HIV-1 coinfected and infected with a closely related strain of HCV genotype 4d...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28059045/computational-screening-of-ccr5-inhibitors-as-potential-entry-inhibitor-microbicides-using-3d-qsar-studies-docking-and-molecular-dynamics-simulation
#4
Radhika Ramachandran, Muthusankar Aathi, D Durairaj Ruban, Shanmughavel Piramanyagam
BACKGROUND: The chemokine receptor CCR5 acts as a co-receptor for HIV binding and it is considered as an important target by CCR5 antagonists. Entry inhibitor based microbicides gain much importance nowadays as these drugs act at an early stage of HIV lifecycle and thus hinder the viral replication process in humans. The present study intends to identify a CCR5 antagonist which could be developed as a microbicide using computational approaches. METHOD: The pharmacophore modeling and 3D QSAR studies was used to identify CCR5 antagonists with enhanced antagonist activity...
January 6, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28053012/phylogenetic-tools-for-generalized-hiv-1-epidemics-findings-from-the-pangea-hiv-methods-comparison
#5
Oliver Ratmann, Emma B Hodcroft, Michael Pickles, Anne Cori, Matthew Hall, Samantha Lycett, Caroline Colijn, Bethany Dearlove, Xavier Didelot, Simon Frost, A S Md Mukarram Hossain, Jeffrey B Joy, Michelle Kendall, Denise Kühnert, Gabriel E Leventhal, Richard Liang, Giacomo Plazzotta, Art F Y Poon, David A Rasmussen, Tanja Stadler, Erik Volz, Caroline Weis, Andrew J Leigh Brown, Christophe Fraser
Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled...
January 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28050723/computational-identification-of-novel-entry-inhibitor-scaffolds-mimicking-primary-receptor-cd4-of-hiv-1-gp120
#6
Alexander M Andrianov, Ivan A Kashyn, Alexander V Tuzikov
Virtual screening of novel entry inhibitor scaffolds mimicking primary receptor CD4 of HIV-1 gp120 was carried out in conjunction with evaluation of their potential inhibitory activity by molecular modeling. To do this, pharmacophore models presenting different sets of the hotspots of cellular receptor CD4 for its interaction with gp120 were generated. These models were used as the templates for identification of CD4-mimetic candidates by the pepMMsMIMIC screening platform. Complexes of these candidates with gp120 were built by high-throughput ligand docking and their stability was estimated by molecular dynamics simulations and binding free energy calculations...
January 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#7
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
January 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28034301/mechanistic-differences-between-hiv-1-and-siv-nucleocapsid-proteins-and-cross-species-hiv-1-genomic-rna-recognition
#8
Klara Post, Erik D Olson, M Nabuan Naufer, Robert J Gorelick, Ioulia Rouzina, Mark C Williams, Karin Musier-Forsyth, Judith G Levin
BACKGROUND: The nucleocapsid (NC) domain of HIV-1 Gag is responsible for specific recognition and packaging of genomic RNA (gRNA) into new viral particles. This occurs through specific interactions between the Gag NC domain and the Psi packaging signal in gRNA. In addition to this critical function, NC proteins are also nucleic acid (NA) chaperone proteins that facilitate NA rearrangements during reverse transcription. Although the interaction with Psi and chaperone activity of HIV-1 NC have been well characterized in vitro, little is known about simian immunodeficiency virus (SIV) NC...
December 29, 2016: Retrovirology
https://www.readbyqxmd.com/read/28029777/nanoscale-characterization-of-interaction-of-apobec3g-with-rna
#9
Yangang Pan, Zhiqiang Sun, Atanu Maiti, Tapan Kanai, Hiroshi Matsuo, Ming Li, Reuben S Harris, Luda S Shlyakhtenko, Yuri L Lyubchenko
The human cytidine deaminase APOBEC3G (A3G) is a potent inhibitor of the HIV-1 virus in the absence of viral infectivity factor (Vif). The molecular mechanism of A3G antiviral activity is primarily attributed to deamination of single-stranded DNA (ssDNA); however the non-deamination mechanism also contributes to HIV-1 restriction. The interaction of A3G with ssDNA and RNA is reguired for its antiviral activity. Here we used atomic force microscopy (AFM) to directly visualize A3G-RNA and A3G-ssDNA complexes and compare to each other...
December 28, 2016: Biochemistry
https://www.readbyqxmd.com/read/28025011/influence-of-raltegravir-intensification-on-viral-load-and-2-ltr-dynamics-in-hiv-patients-on-suppressive-antiretroviral-therapy
#10
Xia Wang, Gregory Mink, Daniel Lin, Xinyu Song, Libin Rong
Antiretroviral therapy can suppress HIV-1 plasma viral load to below the detection limit but cannot eradicate the virus. Whether residual ongoing viral replication persists during suppressive therapy remains unclear. A few clinical studies showed that treatment intensification with an additional drug led to a lower viral load or an increase in 2-LTR (long terminal repeat), a marker for ongoing viral replication. However, some other studies found no change in the viral load and 2-LTR. In this paper, we developed multi-stage models to evaluate the influence of treatment intensification with the integrase inhibitor raltegravir on viral load and 2-LTR dynamics in HIV patients under suppressive therapy...
December 23, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28005684/large-cluster-outbreaks-sustain-the-hiv-epidemic-among-men-having-sex-with-men-msm-in-quebec-from-2002-to-2015
#11
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Isabelle Hardy, David Stephens, Joanne Otis, Erica Moodie, Zehava Grossman, Anne-Mieke Vandamme, Michel Roger, Mark A Wainberg
OBJECTIVE: HIV-1 epidemics among men having sex with men (MSM) remain unchecked despite advances in treatment and prevention paradigms. This study combined viral phylogenetic and behavioural risk data to better understand underlying factors governing the temporal growth of the HIV epidemic among MSM in Quebec (2002-2015). METHODS: Phylogenetic analysis of pol sequences was used to deduce HIV-1 transmission dynamics (cluster size, size distribution and growth rate) in first genotypes of treatment-naïve MSM (2004-2015, n = 3901)...
December 21, 2016: AIDS
https://www.readbyqxmd.com/read/27997613/spatiotemporal-dynamics-of-virus-infection-spreading-in-tissues
#12
Gennady Bocharov, Andreas Meyerhans, Nickolai Bessonov, Sergei Trofimchuk, Vitaly Volpert
Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes...
2016: PloS One
https://www.readbyqxmd.com/read/27994072/hiv-1-latency-reversing-agents-prostratin-and-bryostatin-1-induce-blood-brain-barrier-disruption-inflammation-and-modulate-leukocyte-adhesion-transmigration
#13
Clélia Dental, Alizé Proust, Michel Ouellet, Corinne Barat, Michel J Tremblay
A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3...
December 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27951510/modeling-global-changes-induced-by-local-perturbations-to-the-hiv-1-capsid
#14
Shana Bergman, Timothy R Lezon
The HIV-1 capsid is a conical protein shell made up of hexamers and pentamers of the capsid protein. The capsid houses the viral genome and replication machinery, and its opening, or uncoating, within the host cell marks a critical step in the HIV-1 lifecycle. Binding of host factors such as TRIM5α and cyclophilin A (CypA) can alter the capsid's stability, accelerating or delaying the onset of uncoating and disrupting infectivity. We employ coarse-grained computational modeling to investigate the effects of point mutations and host factor binding on HIV-1 capsid stability...
January 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27930881/ultraslow-domain-motions-in-hiv-1-tar-rna-revealed-by-solid-state-deuterium-nmr
#15
Wei Huang, Prashant S Emani, Gabriele Varani, Gary P Drobny
Intrinsic motions may allow HIV-1 transactivation response (TAR) RNA to change its conformation to form a functional complex with the Tat protein, which is essential for viral replication. Understanding the dynamic properties of TAR necessitates determining motion on the intermediate nanosecond-to-microsecond time scale. To this end, we performed solid-state deuterium NMR line-shape and T1Z relaxation-time experiments to measure intermediate motions for two uridine residues, U40 and U42, within the lower helix of TAR...
December 21, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27927863/longitudinal-viral-dynamics-in-semen-during-early-hiv-infection
#16
Sheldon R Morris, Mitchell Zhao, Davey R Smith, Milenka V Vargas, Susan J Little, Sara Gianella
BACKGROUND: Multiple viruses co-infect the male genital tract, influencing each other's replication and perhaps affecting HIV pathogenesis and disease progression. METHODS: This study included 453 longitudinal seminal samples from 195 HIV-infected men from the San Diego Primary Infection Cohort and 67 seminal samples from HIV-negative healthy controls. Seminal HIV RNA and DNA from seven human herpesviruses (HHV) were measured by RT-PCR. Longitudinal shedding rates were determined by Kaplan-Meier survival analysis...
December 7, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27921997/comparative-molecular-dynamics-study-of-dimeric-and-monomeric-forms-of-hiv-1-protease-in-ligand-bound-and-unbound-state
#17
Monikaben Padariya, Umesh Kalathiya
Human immunodeficiency virus type 1 protease is a viral-encoded enzyme and it is essential for replication and assembly of the virus. Inactivation of HIV-1 protease causes production of immature, noninfectious viral particles and thus HIV-1 protease is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different ligands (COM5 - designed in our previous study, and Darunavir) and made effort to understand dynamics behaviour of our designed compound COM5...
December 6, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27920778/the-dynamics-of-t-and-b-cells-in-lymph-node-during-chronic-hiv-infection-tfh-and-hiv-unhappy-dance-partners
#18
REVIEW
Jung Joo Hong, Kyu-Tae Chang, Francois Villinger
Although the dynamics of germinal center (GC) formation, follicular helper T (TFH) cell recruitment to B cell follicles within lymphoid organs, and changes of lymphoid tissue architecture in HIV/SIV infection have been documented, the underlying immunopathology remains unclear. Here, we summarize what is known regarding the kinetics of TFH cells and GC B cells during the course of infection as well as the potential immunopathological features associated with structural changes in the lymphoid compartment. This review also explores the implications of cell dynamics in the formation and maintenance of viral reservoirs in hyperplastic follicles of secondary lymphoid organs before and after viral suppressive antiretroviral therapy...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27914874/transmission-networks-and-risk-of-hiv-infection-in-kwazulu-natal-south-africa-a-community-wide-phylogenetic-study
#19
Tulio de Oliveira, Ayesha B M Kharsany, Tiago Gräf, Cherie Cawood, David Khanyile, Anneke Grobler, Adrian Puren, Savathree Madurai, Cheryl Baxter, Quarraisha Abdool Karim, Salim S Abdool Karim
BACKGROUND: The incidence of HIV infection in young women in Africa is very high. We did a large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa. METHODS: We did a cross-sectional household survey of randomly selected individuals aged 15-49 years in two neighbouring subdistricts (one urban and one rural) with a high burden of HIV infection in KwaZulu-Natal, South Africa...
January 2017: Lancet HIV
https://www.readbyqxmd.com/read/27907076/clinical-determinants-of-hiv-1b-between-host-evolution-and-their-association-with-drug-resistance-in-pediatric-patients
#20
Israel Pagán, Patricia Rojas, José Tomás Ramos, África Holguín
Understanding the factors that modulate the evolution of virus populations is essential to design efficient control strategies. Mathematical models predict that factors affecting viral within-host evolution may also determine that at the between-host level. Although HIV-1 within-host evolution has been associated with clinical factors used to monitor AIDS progression, such as patient age, CD4 cells count, viral load, and antiretroviral experience, little is known about the role of these clinical factors in determining between-host HIV-1 evolution...
2016: PloS One
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