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HIV viral dynamics

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https://www.readbyqxmd.com/read/29145733/harnessing-novel-imaging-approaches-to-guide-hiv-prevention-and-cure-discoveries-a-national-institutes-of-health-and-global-hiv-vaccine-enterprise-2017-meeting-report
#1
Brigitte Elisabeth Sanders-Beer, Yegor Voronin, David McDonald, Anjali Singh
Advances in imaging technologies have greatly increased our understanding of cellular and molecular interactions in humans and their corresponding animal models of infectious diseases. In the HIV/SIV field, imaging has provided key insights into mucosal viral transmission, local and systemic virus spread, host-virus dynamics, and chronic inflammation/immune activation and the resultant immunopathology. Recent developments in imaging applications are yielding physical, spatial, and temporal measurements to enhance insight into biological functions and disease processes, while retaining important cellular, microenvironmental, organ and intact organism contextual details...
November 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29134249/early-siv-and-hiv-infection-promotes-the-lilrb2-mhc-i-inhibitory-axis-in-cdcs
#2
Lamine Alaoui, Gustavo Palomino, Sandy Zurawski, Gerard Zurawski, Sixtine Coindre, Nathalie Dereuddre-Bosquet, Camille Lecuroux, Cecile Goujard, Bruno Vaslin, Christine Bourgeois, Pierre Roques, Roger Le Grand, Olivier Lambotte, Benoit Favier
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29129570/poly-vinyl-pyrrolidone-lipid-based-hybrid-nanoparticles-for-anti-viral-drug-delivery
#3
K S Joshy, S Snigdha, George Anne, Kalarikkal Nandakumar, Pothen Laly A, Thomas Sabu
Zidovudine (AZT) is an antiviral drug with moderate solubility in water. It has limited application due to its short half life in vivo and consequent requirement for frequent administrations. To solve this problem, zidovudine loaded polyvinylpyrrolidone (PVP)/stearic acid (SA)-polyethylene glycol (PEG) nanoparticles (PSNPs) were developed.The hybrid nanoparticles were prepared by emulsification-solvent evaporation method. The physico chemical characterizations of the PSNPs was done by dynamic light scattering (DLS), transmission electron microscopy (TEM), and fourier transform infra-red spectroscopy (FT-IR)...
November 9, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29122886/mechanism-of-polypurine-tract-primer-generation-by-hiv-1-reverse-transcriptase
#4
Małgorzata Figiel, Miroslav Krepl, Sangwoo Park, Jarosław Poznański, Krzysztof Skowronek, Agnieszka Gołąb, Taekjip Ha, Jiři Šponer, Marcin Nowotny
HIV-1 reverse transcriptase (HIV-1 RT) possesses both DNA polymerase activity and RNase H activity that act in concert to convert single-stranded RNA of the viral genome to double-stranded DNA that is then integrated into the DNA of the infected cell. Reverse transcriptase-catalyzed reverse transcription critically relies on the proper generation of a polypurine tract (PPT) primer. However, the mechanism of PPT primer generation and the features of the PPT sequence that are critical for its recognition by HIV-1 RT remain unclear...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29118123/estimating-initial-viral-levels-during-hiv-siv-reactivation-from-latency
#5
Mykola Pinkevych, Christine M Fennessey, Deborah Cromer, Martin Tolstrup, Ole S Søgaard, Thomas A Rasmussen, Brandon F Keele, Miles P Davenport
HIV viremia rebounds rapidly after treatment interruption, and a variety of strategies are being explored to reduce or control viral reactivation post-treatment. This viral rebound arises from reactivation of individual latently infected cells, which spread during ongoing rounds of productive infection. The level of virus produced by the initial individual reactivating cells is not known, although it may have major implications for the ability of different immune interventions to control viral rebound. Here we use data from both HIV and SIV treatment interruption studies to estimate the initial viral load post-interruption and thereby the initial individual reactivation event...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29117524/cholesterol-promotes-protein-binding-by-affecting-membrane-electrostatics-and-solvation-properties
#6
Milka Doktorova, Frederick A Heberle, Richard L Kingston, George Khelashvili, Michel A Cuendet, Yi Wen, John Katsaras, Gerald W Feigenson, Volker M Vogt, Robert A Dick
Binding of the retroviral structural protein Gag to the cellular plasma membrane is mediated by the protein's matrix (MA) domain. Prominent among MA-PM interactions is electrostatic attraction between the positively charged MA domain and the negatively charged plasma membrane inner leaflet. Previously, we reported that membrane association of HIV-1 Gag, as well as purified Rous sarcoma virus (RSV) MA and Gag, depends strongly on the presence of acidic lipids and is enhanced by cholesterol (Chol). The mechanism underlying this enhancement was unclear...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29114055/immature-hiv-1-lattice-assembly-dynamics-are-regulated-by-scaffolding-from-nucleic-acid-and-the-plasma-membrane
#7
Alexander J Pak, John M A Grime, Prabuddha Sengupta, Antony K Chen, Aleksander E P Durumeric, Anand Srivastava, Mark Yeager, John A G Briggs, Jennifer Lippincott-Schwartz, Gregory A Voth
The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29077766/peripheral-blood-hiv-1-dna-dynamics-in-antiretroviral-treated-hiv-hcv-co-infected-patients-receiving-directly-acting-antivirals
#8
Gabriella Rozera, Gabriele Fabbri, Patrizia Lorenzini, Ilaria Mastrorosa, Laura Timelli, Mauro Zaccarelli, Alessandra Amendola, Alessandra Vergori, Maria Maddalena Plazzi, Stefania Cicalini, Andrea Antinori, Maria Rosaria Capobianchi, Isabella Abbate, Adriana Ammassari
BACKGROUND: Aim was to determine the dynamics of peripheral blood mononuclear cells (PBMC)- associated total HIV-1 DNA in successfully ART-treated HIV/HCV co-infected patients receiving DAA treatment and to explore possible virological hypotheses underlying the phenomenon. METHODS: Longitudinal, single-centre study measuring total HIV-1 DNA before the start of DAA, at the end of treatment (EOT), and 3 months after treatment. Univariable and multivariable analyses were used to assess factors associated with HIV-1 DNA increase ≥0...
2017: PloS One
https://www.readbyqxmd.com/read/29068286/dynamic-hiv-1-genetic-recombination-and-genotypic-drug-resistance-among-treatment-experienced-adults-in-northern-ghana
#9
Nicholas Israel Nii-Trebi, James Ashun Mensah Brandful, Shiro Ibe, Wataru Sugiura, Jacob Samson Barnor, Patrick Owiredu Bampoh, Shoji Yamaoka, Tetsuro Matano, Kazuhisa Yoshimura, Koichi Ishikawa, William Kwabena Ampofo
PURPOSE: There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. METHODOLOGY: A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART...
October 25, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29055819/dynamics-of-lentiviral-infection-in-vivo-in-the-absence-of-adaptive-immune-responses
#10
Elissa J Schwartz, Naveen K Vaidya, Karin S Dorman, Susan Carpenter, Robert H Mealey
Understanding the dynamics of acute viral infection is crucial for developing strategies to prevent and control infection. In this study, lentiviral dynamics in a host without adaptive immunity were examined in order to determine kinetic parameters of infection and quantify the effect of neutralizing antibodies in preventing infection, using mathematical modeling of data from equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Estimated parameters were used to calculate the basic reproductive number and virus doubling time and found that the rate that antibodies neutralized virus was ~18 times greater than the virus clearance rate...
October 19, 2017: Virology
https://www.readbyqxmd.com/read/29055187/an-effective-hiv-1-integrase-inhibitor-screening-platform-rationality-validation-of-drug-screening-conformational-mobility-and-molecular-recognition-analysis-for-pfv-integrase-complex-with-viral-dna
#11
Wenyi Du, Ke Zuo, Xin Sun, Wei Liu, Xiao Yan, Li Liang, Hua Wan, Fengzheng Chen, Jianping Hu
As an important target for the development of novel anti-AIDS drugs, HIV-1 integrase (IN) has been widely concerned. However, the lack of a complete accurate crystal structure of HIV-1 IN greatly blocks the discovery of novel inhibitors. In this work, an effective HIV-1 IN inhibitor screening platform, namely PFV IN, was filtered from all species of INs. Next, the 40.8% similarity with HIV-1 IN, as well as the high efficiency of virtual screening and the good agreement between calculated binding free energies and experimental ones all proved PFV IN is a promising screening platform for HIV-1 IN inhibitors...
October 5, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29049331/hiv-dynamics-linked-to-memory-cd4-t-cell-homeostasis
#12
John M Murray, John Zaunders, Sean Emery, David A Cooper, William J Hey-Nguyen, Kersten K Koelsch, Anthony D Kelleher
The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART...
2017: PloS One
https://www.readbyqxmd.com/read/29045592/impact-of-public-safety-policies-on-hiv-transmission-dynamics-in-tijuana-mexico
#13
Sanjay R Mehta, Antoine Chaillon, Tommi L Gaines, Patricia E Gonzalez-Zuniga, Jamila K Stockman, Horatio Almanza-Reyes, Jose Roman Chavez, Alicia Vera, Karla D Wagner, Thomas L Patterson, Brianna Scott, Davey M Smith, Steffanie A Strathdee
Background: North Tijuana, Mexico, along the US border, is home to many individuals at high-risk for transmitting and acquiring HIV. Recently, policy shifts by local government impacted how these individuals were handled by authorities. Here we examined how this affected regional HIV transmission dynamics. Methods: HIV pol sequences and associated demographic information were collected from eight research studies enrolling persons in Tijuana, and were used to infer viral transmission patterns and transmission clusters...
October 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29028657/combinations-of-interventions-to-achieve-a-national-hiv-incidence-reduction-goal-insights-from-an-agent-based-model
#14
Chaitra Gopalappa, Stephanie L Sansom, Paul G Farnham, Yao-Hsuan Chen
OBJECTIVE: Analyzing HIV care service targets for achieving a national goal of a 25% reduction in annual HIV incidence and evaluating the use of annual HIV diagnoses to measure progress in incidence reduction. DESIGN: Because there are considerable interactions among HIV care services, we model the dynamics of 'combinations' of increases in HIV care continuum targets to identify those that would achieve 25% reductions in annual incidence and diagnoses. METHODS: We used Progression and Transmission of HIV/AIDS 2...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/28991889/trends-in-drug-resistance-prevalence-hiv-1-variants-and-clinical-status-in-hiv-1-infected-pediatric-population-in-madrid-1993-2015-analysis
#15
Patricia Rojas Sánchez, Sara Domínguez, Santiago Jiménez De Ory, Luis Prieto, Pablo Rojo, Pepa Mellado, Marisa Navarro, Rafael Delgado, José Tomas Ramos, África Holguín
BACKGROUND: The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations (HIVDR) selection, which can compromise treatment efficiency. OBJECTIVE: We describe the temporal trends of HIVDR and the HIV-1 variants during 23 years (1993-March 2016) in the Madrid cohort of HIV-infected children and adolescents. METHODS: We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data...
October 6, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28981470/telomere-dynamics-in-immune-senescence-and-exhaustion-triggered-by-chronic-viral-infection
#16
REVIEW
Marcia Bellon, Christophe Nicot
The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics...
October 5, 2017: Viruses
https://www.readbyqxmd.com/read/28978711/functional-stability-of-hiv-1-envelope-trimer-affects-accessibility-to-broadly-neutralizing-antibodies-at-its-apex
#17
Syna Kuriakose Gift, Daniel P Leaman, Lei Zhang, Arthur S Kim, Michael B Zwick
The trimeric envelope glycoprotein spike (Env) of HIV-1 is the target of vaccine development to elicit broadly neutralizing antibodies (bnAbs). Env trimer instability and heterogeneity in principle make subunit interfaces inconsistent targets for the immune response. Here, we investigate how functional stability of Env relates to neutralization sensitivity to V2 bnAbs and V3 crown antibodies that engage subunit interfaces upon binding to unliganded Env. Env heterogeneity was inferred when antibodies neutralized a mutant Env with a plateau of less than 100% percentage neutralization...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28971331/resting-state-functional-magnetic-resonance-imaging-in-clade-c-hiv-within-group-association-with-neurocognitive-function
#18
Lindie du Plessis, Robert H Paul, Jackie Hoare, Dan J Stein, Paul A Taylor, Ernesta M Meintjes, John A Joska
Neuroimaging abnormalities are common in chronically infected HIV-positive individuals. The majority of studies have focused on structural or functional brain outcomes in samples infected with clade B HIV. While preliminary work reveals a similar structural imaging phenotype in patients infected with clade C HIV, no study has examined functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI) in clade C HIV. In particular, we were interested to explore HIV-only effects on neurocognitive function using associations with rs-fMRI...
October 2, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28970973/multi-scale-immunoepidemiological-modeling-of-within-host-and-between-host-hiv-dynamics-systematic-review-of-mathematical-models
#19
Nargesalsadat Dorratoltaj, Ryan Nikin-Beers, Stanca M Ciupe, Stephen G Eubank, Kaja M Abbas
OBJECTIVE: The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level. BACKGROUND: While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels...
2017: PeerJ
https://www.readbyqxmd.com/read/28953921/virological-and-immunological-outcome-of-treatment-interruption-in-hiv-1-infected-subjects-vaccinated-with-mva-b
#20
Miriam Rosás-Umbert, Beatriz Mothe, Marc Noguera-Julian, Rocío Bellido, Maria C Puertas, Jorge Carrillo, C Rodriguez, Núria Perez-Alvarez, Patricia Cobarsí, Carmen E Gomez, Mariano Esteban, Jose Luis Jímenez, Felipe García, Julià Blanco, Javier Martinez-Picado, Roger Paredes, Christian Brander
The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control...
2017: PloS One
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