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HIV viral dynamics

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https://www.readbyqxmd.com/read/28931691/vertical-transmission-of-hepatitis-c-virus-variable-transmission-bottleneck-and-evidence-of-mid-gestation-in-utero-infection
#1
Sébastien Fauteux-Daniel, Ariane Larouche, Virginie Calderon, Jonathan Boulais, Chanel Béland, Doris G Ransy, Marc Boucher, Valérie Lamarre, Normand Lapointe, Isabelle Boucoiran, Armelle Le Campion, Hugo Soudeyns
Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biologic mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with HIV-1. The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491-1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median joining network analysis...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931681/insights-into-the-impact-of-cd8-immune-modulation-on-hiv-evolutionary-dynamics-in-distinct-anatomical-compartments-using-siv-infected-macaque-models-of-aids-progression
#2
Brittany Rife Magalis, David J Nolan, Patrick Autissier, Tricia H Burdo, Kenneth C Williams, Marco Salemi
A thorough understanding of the role of HIV intra-host evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8+ lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to similar clinical manifestations as HIV-1 infection and AIDS progression, as well as characteristic rapid disease onset...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28916807/envelope-glycoprotein-mobility-on-hiv-1-particles-depends-on-the-virus-maturation-state
#3
Jakub Chojnacki, Dominic Waithe, Pablo Carravilla, Nerea Huarte, Silvia Galiani, Jörg Enderlein, Christian Eggeling
Human immunodeficiency virus type 1 (HIV-1) assembles as immature particles, which require the proteolytic cleavage of structural polyprotein Gag and the clustering of envelope glycoprotein Env for infectivity. The details of mechanisms underlying Env clustering remain unknown. Here, we determine molecular dynamics of Env on the surface of individual HIV-1 particles using scanning fluorescence correlation spectroscopy on a super-resolution STED microscope. We find that Env undergoes a maturation-induced increase in mobility, highlighting diffusion as one cause for Env clustering...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#4
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28894444/modeling-kick-kill-strategies-toward-hiv-cure
#5
REVIEW
Esteban A Hernandez-Vargas
Although combinatorial antiretroviral therapy (cART) potently suppresses the virus, a sterile or functional cure still remains one of the greatest therapeutic challenges worldwide. Reservoirs are infected cells that can maintain HIV persistence for several years in patients with optimal cART, which is a leading obstacle to eradicate the virus. Despite the significant progress that has been made in our understanding of the diversity of cells that promote HIV persistence, many aspects that are critical to the development of effective therapeutic approaches able to purge the latent CD4+ T cell reservoir are poorly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28893602/raltegravir-blocks-the-infectivity-of-red-fluorescent-protein-mcherry-labeled-hiv-1jr-fl-in-the-setting-of-post-exposure-prophylaxis-in-nod-scid-jak3-mice-transplanted-with-human-pbmcs
#6
Hiromi Ogata-Aoki, Nobuyo Higashi-Kuwata, Shin-Ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Yumi Hashiguchi, Akinobu Hamada, Hisataka Kobayashi, Hironobu Ihn, Seiji Okada, Hiroaki Mitsuya
Employing NOD/SCID/Jak3(-/-) mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1JR-FL (HIVmC), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIVmC enabled us to visually locate infection foci and to examine the early dynamics of HIVmC infection without using a large amount of antiretroviral unlike in non-human primate models. Although when raltegravir (RAL) administration was begun 1 day after intraperitoneal (ip) inoculation of HIVmC, no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJmC(RAL+)) mice over 14-day observation, all 10 untreated hNOJmC (hNOJmC(RAL-)) mice became positive for p24 and pRNA and had significantly swollen lymph nodes in peritoneal cavity and abundant p24(+)/mC(+)/CD3(+)/CD4(+) T cells and p24(+)/mC(+)/CD68(+) monocytes/macrophages were identified in their omenta and mesenteric lymphoid tissues/lymph nodes...
September 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28874142/risk-factors-for-increased-immune-reconstitution-in-response-to-mycobacterium-tuberculosis-antigens-in-tuberculosis-hiv-infected-antiretroviral-na%C3%A3-ve-patients
#7
Tatiana Pereira da Silva, Carmem Beatriz Wagner Giacoia-Gripp, Carolina A Schmaltz, Flavia Marinho Sant'Anna, Maria Helena Saad, Juliana Arruda de Matos, Julio Castro Alves de Lima E Silva, Valeria Cavalcanti Rolla, Mariza Gonçalves Morgado
BACKGROUND: Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution...
September 6, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28857823/perceived-and-post-traumatic-stress-are-associated-with-decreased-learning-memory-and-fluency-in-hiv-infected-women
#8
Leah H Rubin, Judith A Cook, Gayle Springer, Kathleen M Weber, Mardge H Cohen, Eileen M Martin, Victor G Valcour, Lorie Benning, Christine Alden, Joel Milam, Kathryn Anastos, Mary A Young, Deborah R Gustafson, Erin E Sundermann, Pauline M Maki
OBJECTIVE: Psychological risk factors (PRFs) are associated with impaired learning and memory in HIV-infected (HIV+) women. We determined the dynamic nature of the effects of PRFs and HIV serostatus on learning and memory over time. DESIGN: Multi-center, prospective cohort study METHODS:: Every two years between 2009 and 2013 (3 times), 646 HIV+ and 300 demographically-similar HIV-uninfected (HIV-) women from the Women's Interagency HIV Study completed neuropsychological (NP) testing and questionnaires measuring PRFs (perceived stress, post-traumatic stress disorder (PTSD) symptoms, depressive symptoms)...
August 28, 2017: AIDS
https://www.readbyqxmd.com/read/28852573/biased-phylodynamic-inferences-from-analysing-clusters-of-viral-sequences
#9
Bethany L Dearlove, Fei Xiang, Simon D W Frost
Phylogenetic methods are being increasingly used to help understand the transmission dynamics of measurably evolving viruses, including HIV. Clusters of highly similar sequences are often observed, which appear to follow a 'power law' behaviour, with a small number of very large clusters. These clusters may help to identify subpopulations in an epidemic, and inform where intervention strategies should be implemented. However, clustering of samples does not necessarily imply the presence of a subpopulation with high transmission rates, as groups of closely related viruses can also occur due to non-epidemiological effects such as over-sampling...
July 2017: Virus Evolution
https://www.readbyqxmd.com/read/28841647/probing-the-compartmentalization-of-hiv-1-in-the-central-nervous-system-through-its-neutralization-properties
#10
Karl Stefic, Antoine Chaillon, Mélanie Bouvin-Pley, Alain Moreau, Martine Braibant, Frédéric Bastides, Guillaume Gras, Louis Bernard, Francis Barin
Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28838149/human-immunodeficiency-virus-type-1-persistence-following-systemic-chemotherapy-for-malignancy
#11
Timothy J Henrich, Kristen S Hobbs, Emily Hanhauser, Eileen Scully, Louise E Hogan, Yvonne P Robles, Kaitlyn S Leadabrand, Francisco M Marty, Christine D Palmer, Stephanie Jost, Christian Körner, Jonathan Z Li, Rajesh T Gandhi, Ayad Hamdan, Jeremy Abramson, Ann S LaCasce, Daniel R Kuritzkes
Background: Systemic chemotherapies for various malignancies have been shown to significantly, yet transiently, decrease numbers of CD4+ T lymphocytes, a major reservoir for human immunodeficiency virus type 1 (HIV-1) infection. However, little is known about the impact of cytoreductive chemotherapy on HIV-1 reservoir dynamics, persistence, and immune responses. Methods: We investigated the changes in peripheral CD4+ T-cell-associated HIV-1 DNA and RNA levels, lymphocyte activation, viral population structure, and virus-specific immune responses in a longitudinal cohort of 15 HIV-1-infected individuals receiving systemic chemotherapy or subsequent autologous stem cell transplantation for treatment of hematological malignancies and solid tumors...
July 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28827840/dynamics-and-regulation-of-nuclear-import-and-nuclear-movements-of-hiv-1-complexes
#12
Ryan C Burdick, Krista A Delviks-Frankenberry, Jianbo Chen, Sanath K Janaka, Jaya Sastri, Wei-Shau Hu, Vinay K Pathak
The dynamics and regulation of HIV-1 nuclear import and its intranuclear movements after import have not been studied. To elucidate these essential HIV-1 post-entry events, we labeled viral complexes with two fluorescently tagged virion-incorporated proteins (APOBEC3F or integrase), and analyzed the HIV-1 dynamics of nuclear envelope (NE) docking, nuclear import, and intranuclear movements in living cells. We observed that HIV-1 complexes exhibit unusually long NE residence times (1.5±1.6 hrs) compared to most cellular cargos, which are imported into the nuclei within milliseconds...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28814526/hiv-1-exploits-dynamic-multi-aminoacyl-trna-synthetase-complex-to-enhance-viral-replication
#13
Alice A Duchon, Corine St-Gelais, Nathan Titkemeier, Joshua Hatterschide, Li Wu, Karin Musier-Forsyth
A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA(Lys3) to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28802027/performance-evaluation-of-the-bioneer-accupower%C3%A2-hiv-1-quantitative-rt-pcr-kit-comparison-with-the-roche-cobas%C3%A2-ampliprep-cobas-taqman%C3%A2-hiv-1-test-ver-2-0-for-quantification-of-hiv-1-viral-load-in-indonesia
#14
Agus Susanto Kosasih, Christine Sugiarto, Hubertus Hosti Hayuanta, Runingsih Juhaendi, Lyana Setiawan
BACKGROUND: Measurement of viral load in human immunodeficiency virus type 1 (HIV-1) infected patients is essential for the establishment of a therapeutic strategy. Several assays based on qPCR are available for the measurement of viral load; they differ in sample volume, technology applied, target gene, sensitivity and dynamic range. The Bioneer AccuPower® HIV-1 Quantitative RT-PCR is a novel commercial kit that has not been evaluated for its performance. OBJECTIVE: This study aimed to evaluate the performance of the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit...
August 8, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/28791894/decoding-hiv-resistance-from-genotype-to-therapy
#15
Irene T Weber, Robert W Harrison
Genetic variation in HIV poses a major challenge for prevention and treatment of the AIDS pandemic. Resistance occurs by mutations in the target proteins that lower affinity for the drug or alter the protein dynamics, thereby enabling viral replication in the presence of the drug. Due to the prevalence of drug-resistant strains, monitoring the genotype of the infecting virus is recommended. Computational approaches for predicting resistance from genotype data and guiding therapy are discussed. Many prediction methods rely on rules derived from known resistance-associated mutations, however, statistical or machine learning can improve the classification accuracy and assess unknown mutations...
August 9, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28762130/modelling-coupled-within-host-and-population-dynamics-of-formula-see-text-and-formula-see-text-hiv-infection
#16
Edna Chilenje Manda, Faraimunashe Chirove
Most existing models have considered the immunological processes occurring within the host and the epidemiological processes occurring at population level as decoupled systems. We present a new model using continuous systems of non linear ordinary differential equations by directly linking the within host dynamics capturing the interactions between Langerhans cells, CD4[Formula: see text] T-cells, R5 HIV and X4 HIV and the without host dynamics of a basic compartmental HIV/AIDS model. The model captures the biological theories of the cells that take part in HIV transmission...
July 31, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28761140/dynamics-and-mechanisms-of-clonal-expansion-of-hiv-1-infected-cells-in-a-humanized-mouse-model
#17
Yorifumi Satou, Hiroo Katsuya, Asami Fukuda, Naoko Misawa, Jumpei Ito, Yoshikazu Uchiyama, Paola Miyazato, Saiful Islam, Ariberto Fassati, Anat Melamed, Charles R M Bangham, Yoshio Koyanagi, Kei Sato
Combination anti-retroviral therapy (cART) has drastically improved the clinical outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in peripheral blood has been reported recently. cART is effective in stopping the retroviral replication cycle, but not in inhibiting clonal expansion of the infected host cells. Thus, the proliferation of HIV-1-infected cells may play a role in viral persistence, but little is known about the kinetics of the generation, the tissue distribution or the underlying mechanism of clonal expansion in vivo...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28750647/high-level-of-hiv-1-drug-resistance-mutations-in-patients-with-unsuppressed-viral-loads-in-rural-northern-south-africa
#18
Elizabeth M Etta, Lufuno Mavhandu, Cecile Manhaeve, Keanan McGonigle, Patrick Jackson, David Rekosh, Marie-Louise Hammarskjold, Pascal O Bessong, Denis M Tebit
BACKGROUND: Combination antiretroviral therapy (cART) has significantly reduced HIV morbidity and mortality in both developed and developing countries. However, the sustainability of cART may be compromised by the emergence of viral drug resistance mutations (DRM) and the cellular persistence of proviruses carrying these DRM. This is potentially a more serious problem in resource limited settings. METHODS: DRM were evaluated in individuals with unsuppressed viral loads after first or multiple lines of cART at two sites in rural Limpopo, South Africa...
July 27, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28738861/the-risk-of-hiv-transmission-at-each-step-of-the-hiv-care-continuum-among-people-who-inject-drugs-a-modeling-study
#19
Daniel J Escudero, Mark N Lurie, Kenneth H Mayer, Maximilian King, Sandro Galea, Samuel R Friedman, Brandon D L Marshall
BACKGROUND: People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID. METHODS: We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012...
July 25, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28695547/human-immunodeficiency-virus-promotes-mitochondrial-toxicity
#20
REVIEW
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Margarita Trejo, Hoai T Ton, Gerard P Ahern, Italo Mocchetti
Combined antiretroviral therapies (cART) have had remarkable success in reducing morbidity and mortality among patients infected with human immunodeficiency virus (HIV). However, mild forms of HIV-associated neurocognitive disorders (HAND), characterized by loss of synapses, remain. cART may maintain an undetectable HIV RNA load but does not eliminate the expression of viral proteins such as trans-activator of transcription (Tat) and the envelope glycoprotein gp120 in the brain. These two viral proteins are known to promote synaptic simplifications by several mechanisms, including alteration of mitochondrial function and dynamics...
July 10, 2017: Neurotoxicity Research
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