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https://www.readbyqxmd.com/read/28727817/immunogenicity-of-a-novel-clade-b-hiv-1-vaccine-combination-results-of-phase-1-randomized-placebo-controlled-trial-of-an-hiv-1-gm-csf-expressing-dna-prime-with-a-modified-vaccinia-ankara-vaccine-boost-in-healthy-hiv-1-uninfected-adults
#1
Susan P Buchbinder, Nicole A Grunenberg, Brittany J Sanchez, Kelly E Seaton, Guido Ferrari, M Anthony Moody, Nicole Frahm, David C Montefiori, Christine M Hay, Paul A Goepfert, Lindsey R Baden, Harriet L Robinson, Xuesong Yu, Peter B Gilbert, M Juliana McElrath, Yunda Huang, Georgia D Tomaras
BACKGROUND: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. METHODS: Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#2
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28726743/the-effect-of-n-terminal-cyclization-on-the-function-of-the-hiv-entry-inhibitor-5p12-rantes
#3
Anna F Nguyen, Megan S Schill, Mike Jian, Patricia J LiWang
Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28725563/atypical-hemolytic-uremic-syndrome-triggered-by-varicella-infection
#4
Pauline Condom, Jean-Michel Mansuy, Stéphane Decramer, Jacques Izopet, Catherine Mengelle
Varicella Zoster Virus (VZV) is a well-known virus that belongs to the Herpesviridae family which induces a self-limited disease except in specific cases in particular among stem cell transplant patients. This virus is not known however to trigger atypical Hemolytic Uremic Syndrome (aHUS). Here we report the case of a six-year-old boy who was hospitalized with fever and abdominal pains associated to pruritic and vesicular rash, thrombocytopenia and acute renal failure. He was diagnosed with aHUS precipitated by varicella virus...
2017: IDCases
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#5
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28725166/tuberculosis-and-hiv-are-the-leading-causes-of-adult-death-in-northwest-ethiopia-evidence-from-verbal-autopsy-data-of-dabat-health-and-demographic-surveillance-system-2007-2013
#6
Yigzaw Kebede, Gashaw Andargie, Abebaw Gebeyehu, Tadesse Awoke, Mezgebu Yitayal, Solomon Mekonnen, Mamo Wubshet, Temesgen Azmeraw, Yihunie Lakew, Kassahun Alemu
BACKGROUND: Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system...
2017: Population Health Metrics
https://www.readbyqxmd.com/read/28724368/utilizing-patient-data-from-the-veterans-administration-electronic-health-record-to-support-web-based-clinical-decision-support-informatics-challenges-and-issues-from-three-clinical-domains
#7
Nallakkandi Rajeevan, Kristina M Niehoff, Peter Charpentier, Forrest L Levin, Amy Justice, Cynthia A Brandt, Terri R Fried, Perry L Miller
BACKGROUND: The US Veterans Administration (VA) has developed a robust and mature computational infrastructure in support of its electronic health record (EHR). Web technology offers a powerful set of tools for structuring clinical decision support (CDS) around clinical care. This paper describes informatics challenges and design issues that were confronted in the process of building three Web-based CDS systems in the context of the VA EHR. METHODS: Over the course of several years, we implemented three Web-based CDS systems that extract patient data from the VA EHR environment to provide patient-specific CDS...
July 19, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28723963/impact-of-thyroid-function-abnormalities-on-reproductive-hormones-during-menstrual-cycle-in-premenopausal-hiv-infected-females-at-nauth-nnewi-nigeria
#8
Nkiruka Rose Ukibe, Solomon Nwabueze Ukibe, Obiageli Fidelia Emelumadu, Chinedum Charles Onyenekwe, Joseph Eberendu Ahaneku, Anthony Osita Igwegbe, Ifeoma Nwamaka Monago, Amobi Linus Ilika
BACKGROUND: This was a prospective study designed to evaluate the impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in HIV infected females at Nnamdi Azikiwe University Teaching Hospital Nnewi, South-East Nigeria. METHODS: The study randomly recruited 35 Symptomatic HIV infected females and 35 Symptomatic HIV infected females on antiretroviral therapy (HAART) for not less than six weeks from an HIV clinic and 40 apparently heathy control females among the hospital staff of NAUTH Nnewi...
2017: PloS One
https://www.readbyqxmd.com/read/28722475/ann-qsar-workflow-for-predicting-the-inhibition-of-hiv-1-reverse-transcriptase-by-pyridinone-non-nucleoside-derivatives
#9
Abolfazl Barzegar, Elham Zamani-Gharehchamani, Ali Kadkhodaie-Ilkhchi
AIM: Pyridinone derivatives have high potency against non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type-1 strains. Quantitative structure-activity relationship (QSAR) studies on a series of pyridinone derivatives acting as NNRTIs are very important in designing the next generation of NNRTIs. Methodology & results: The QSAR models were developed using linear (single and forward stepwise) and combined nonlinear artificial neural network (ANN) approaches...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722007/physical-properties-of-the-hiv-1-capsid-from-all-atom-molecular-dynamics-simulations
#10
Juan R Perilla, Klaus Schulten
Human immunodeficiency virus type 1 (HIV-1) infection is highly dependent on its capsid. The capsid is a large container, made of ∼1,300 proteins with altogether 4 million atoms. Although the capsid proteins are all identical, they nevertheless arrange themselves into a largely asymmetric structure made of hexamers and pentamers. The large number of degrees of freedom and lack of symmetry pose a challenge to studying the chemical details of the HIV capsid. Simulations of over 64 million atoms for over 1 μs allow us to conduct a comprehensive study of the chemical-physical properties of an empty HIV-1 capsid, including its electrostatics, vibrational and acoustic properties, and the effects of solvent (ions and water) on the capsid...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28721049/the-potential-role-of-vagus-nerve-stimulation-in-the-treatment-of-hiv-associated-depression-a-review-of-literature
#11
REVIEW
William C Nicholson, Mirjam-Colette Kempf, Linda Moneyham, David E Vance
Depression is the most common comorbidity and neuropsychiatric complication in HIV. Estimates suggest that the prevalence rate for depression among HIV-infected individuals is three times that of the general population. The association between HIV and clinical depression is complex; however, chronic activation of inflammatory mechanisms, which disrupt central nervous system (CNS) function, may contribute to this association. Disruptions in CNS function can result in cognitive disorders, social withdrawal, fatigue, apathy, psychomotor impairment, and sleep disturbances, which are common manifestations in depression and HIV alike...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28720122/enhance-the-performance-of-current-scoring-functions-with-the-aid-of-3d-protein-ligand-interaction-fingerprints
#12
Jie Liu, Minyi Su, Zhihai Liu, Jie Li, Yan Li, Renxiao Wang
BACKGROUND: In structure-based drug design, binding affinity prediction remains as a challenging goal for current scoring functions. Development of target-biased scoring functions provides a new possibility for tackling this problem, but this approach is also associated with certain technical difficulties. We previously reported the Knowledge-Guided Scoring (KGS) method as an alternative approach (BMC Bioinformatics, 2010, 11, 193-208). The key idea is to compute the binding affinity of a given protein-ligand complex based on the known binding data of an appropriate reference complex, so the error in binding affinity prediction can be reduced effectively...
July 18, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#13
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#14
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28717424/low-active-loading-of-cargo-into-engineered-extracellular-vesicles-results-in-inefficient-mirna-mimic-delivery
#15
Dhruvitkumar S Sutaria, Jinmai Jiang, Ola A Elgamal, Steven M Pomeroy, Mohamed Badawi, Xiaohua Zhu, Ryan Pavlovicz, Ana Clara P Azevedo-Pouly, Jeffrey Chalmers, Chenglong Li, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28716964/a-glun2b-selective-nmdar-antagonist-reverses-synapse-loss-and-cognitive-impairment-produced-by-the-hiv-1-protein-tat
#16
Jonathan D Raybuck, Nicholas J Hargus, Stanley A Thayer
HIV-associated neurocognitive disorder (HAND) affects approximately half of HIV-infected patients. Loss of synaptic connections is a hallmark of many neurocognitive disorders, including HAND. The HIV-1 protein transactivator of transcription (Tat) disrupts synaptic connections both in vitro and in vivo and has been linked to impaired neurocognitive function in humans. In vitro studies have shown that ifenprodil, an antagonist selective for GluN2B-containing NMDARs, reverses synapse loss when applied after Tat...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716545/effect-of-ageing-on-neurocognitive-function-by-stage-of-hiv-infection-evidence-from-the-multicenter-aids-cohort-study
#17
Karl Goodkin, Eric N Miller, Christopher Cox, Sandra Reynolds, James T Becker, Eileen Martin, Ola A Selnes, David G Ostrow, Ned C Sacktor
BACKGROUND: The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. METHODS: With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function...
July 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28716042/tuberculosis-and-hiv-are-the-leading-causes-of-adult-death-in-northwest-ethiopia-evidence-from-verbal-autopsy-data-of-dabat-health-and-demographic-surveillance-system-2007-2013
#18
Yigzaw Kebede, Gashaw Andargie, Abebaw Gebeyehu, Tadesse Awoke, Mezgebu Yitayal, Solomon Mekonnen, Mamo Wubshet, Temesgen Azmeraw, Yihunie Lakew, Kassahun Alemu
BACKGROUND: Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system...
July 17, 2017: Population Health Metrics
https://www.readbyqxmd.com/read/28715971/a-consensus-view-of-escrt-mediated-human-immunodeficiency-virus-type-1-abscission
#19
J Lippincott-Schwartz, E O Freed, S B van Engelenburg
The strong dependence of retroviruses, such as human immunodeficiency virus type 1 (HIV-1), on host cell factors is no more apparent than when the endosomal sorting complex required for transport (ESCRT) machinery is purposely disengaged. The resulting potent inhibition of retrovirus release underscores the importance of understanding fundamental structure-function relationships at the ESCRT-HIV-1 interface. Recent studies utilizing advanced imaging technologies have helped clarify these relationships, overcoming hurdles to provide a range of potential models for ESCRT-mediated virus abscission...
July 17, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28713164/human-immunodeficiency-virus-type-1-induces-a-regulatory-b-cell-like-phenotype-in-vitro
#20
Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Maria-Ángeles Muñoz-Fernandez, Rafael Correa-Rocha, Marjorie Pion
Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells...
July 17, 2017: Cellular & Molecular Immunology
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