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https://www.readbyqxmd.com/read/28209172/evaluation-of-the-contribution-of-the-transmembrane-region-to-the-ectodomain-conformation-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein
#1
Hanh T Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C Kappes, Youdong Mao, Joseph G Sodroski
BACKGROUND: The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts...
February 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28207490/how-hiv-1-entry-mechanism-and-broadly-neutralizing-antibodies-guide-structure-based-vaccine-design
#2
Marie Pancera, Anita Changela, Peter D Kwong
PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies (bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1 entry mechanism is guiding the structure-based design of vaccine immunogens and immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected donors has led to an unprecedented understanding of the sites of vulnerability that these antibodies target on the HIV-1 envelope (Env) as well as of the immunological pathways that these antibody lineages follow to develop broad and potent neutralization...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28194688/emergency-department-initiated-buprenorphine-for-opioid-dependence-with-continuation-in-primary-care-outcomes-during-and-after-intervention
#3
Gail D'Onofrio, Marek C Chawarski, Patrick G O'Connor, Michael V Pantalon, Susan H Busch, Patricia H Owens, Kathryn Hawk, Steven L Bernstein, David A Fiellin
BACKGROUND: Emergency department (ED)-initiated buprenorphine/naloxone with continuation in primary care was found to increase engagement in addiction treatment and reduce illicit opioid use at 30 days compared to referral only or a brief intervention with referral. OBJECTIVE: To evaluate the long-term outcomes at 2, 6 and 12 months following ED interventions. DESIGN: Evaluation of treatment engagement, drug use, and HIV risk among a cohort of patients from a randomized trial who completed at least one long-term follow-up assessment...
February 13, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28193659/oligonucleotide-lipid-conjugates-forming-g-quadruplex-structures-are-potent-and-pangenotypic-hepatitis-c-virus-entry-inhibitors-in-vitro-and-ex-vivo
#4
George Koutsoudakis, Alexia Paris de León, Carolina Herrera, Marcus Dorner, Gemma Pérez-Vilaró, Sébastien Lyonnais, Santiago Grijalvo, Ramon Eritja, Andreas Meyerhans, Gilles Mirambeau, Juana Díez
An HCV epidemic affecting HIV-infected men who have sex with men (MSM) is expanding worldwide. Albeit the improved cure rates obtained with the new direct-acting antiviral drug (DAA) combinations, the high rate of reinfection within this population calls urgently for novel preventive interventions. Here we show in cell culture and ex vivo experiments with human colorectal tissue that lipoquads, G-quadruplex DNA structures fused to cholesterol, are efficient HCV pangenotypic entry and cell-to-cell transmission inhibitors...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28185620/pulmonary-tuberculosis
#5
Sarah M Lyon, Milton D Rossman
This review on pulmonary tuberculosis includes an introduction that describes how the lung is the portal of entry for the tuberculosis bacilli to enter the body and then spread to the rest of the body. The symptoms and signs of both primary and reactivation tuberculosis are described. Routine laboratory tests are rarely helpful for making the diagnosis of tuberculosis. The differences between the chest X ray in primary and reactivation tuberculosis is also described. The chest computed tomography appearance in primary and reactivation tuberculosis is also described...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28177261/stability-of-5p12-rantes-a-candidate-rectal-microbicide-in-human-rectal-lavage
#6
Fabrice Cerini, Robin E Offord, Ian McGowan, Oliver Hartley
In the absence of an effective vaccine, strategies to prevent HIV transmission are urgently needed. Condomless receptive anal intercourse represents a major route of transmission, and efforts are being made to develop strategies in which potent anti-HIV drugs are formulated for topical application to the rectum prior to sex. 5P12-RANTES is a promising candidate for such a purpose. It is an analogue of the human chemokine RANTES/CCL5, which potently blocks CCR5, the principal coreceptor used by HIV to enter and infect target cells...
February 8, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28166380/nmr-insights-into-the-conformational-properties-of-man-9-and-its-recognition-by-two-hiv-binding-proteins
#7
Syed Shahzad-Ul-Hussan, Mallika Sastry, Thomas Lemmin, Cinque Soto, Sandra Loesgen, Danielle A Scott, Jack Robert Davison, Robert O'Connor, Peter D Kwong, Carole A Bewley
Man9GlcNAc2 (Man-9) present at the surface of HIV constitutes the binding sites of several HIV neutralizing agents and mammalian lectin DC-SIGN that is involved in cellular immunity and trans-infections. We describe the conformational properties of Man-9 in free state and when bound by an HIV entry inhibitor protein and define the minimum epitopes of two HIV binding proteins using NMR spectroscopy. In this regard we developed a robust expression system for production of 13C,15N-labeled glycans in mammalian cells that facilitated the implementation of 3D 13C-edited spectra to deconvolute spectral overlap allowing for the solution structure determination of Man-9...
February 6, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28164028/the-clinical-spectrum-of-severe-acute-malnutrition-in-children-in-cameroon-a-hospital-based-study-in-yaounde-cameroon
#8
Andreas Chiabi, Berthe Malangue, Seraphin Nguefack, Félicitée Nguefack Dongmo, Florence Fru, Virginie Takou, Fru Angwafo
BACKGROUND: Severe acute malnutrition (SAM) is a major health problem, and the cause of more than half of childhood deaths in children less than 5 years in developing countries. Globally, 20 million children under 5 years of age are severely malnourished according to the World Health Organization (WHO). In Cameroon, the prevalence of SAM remains high and estimated at 1.9% in 2011 and 1.3% in 2014. The aim of this study was to determine the epidemiology, clinical aspects and outcome of SAM at the Yaounde Gynaeco-Obstetric and Pediatric Hospital (YGOPH)...
January 2017: Translational pediatrics
https://www.readbyqxmd.com/read/28151945/antigenic-characterization-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein-precursor-incorporated-into-nanodiscs
#9
Kristen C Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C Kappes, Joseph Sodroski
The entry of human immunodeficiency virus (HIV-1) into host cells is mediated by the viral envelope glycoproteins (Envs), which are derived by the proteolytic cleavage of a trimeric gp160 Env precursor. The mature Env trimer is a major target for entry inhibitors and vaccine-induced neutralizing antibodies. Env interstrain variability, conformational flexibility and heavy glycosylation contribute to evasion of the host immune response, and create challenges for structural characterization and vaccine development...
2017: PloS One
https://www.readbyqxmd.com/read/28149649/hepatitis-c-virus-infection-and-neurological-and-psychiatric-disorders-a-review
#10
REVIEW
Lydia Yarlott, Eleanor Heald, Daniel Forton
An association between hepatitis C virus infection and neuropsychiatric symptoms has been proposed for some years. A variety of studies have been undertaken to assess the nature and severity of these symptoms, which range from fatigue and depression to defects in attention and verbal reasoning. There is evidence of mild neurocognitive impairment in some patients with HCV infection, which is not fully attributable to liver dysfunction or psychosocial factors. Further evidence of a biological cerebral effect has arisen from studies using magnetic resonance spectroscopy; metabolic abnormalities correlate with cognitive dysfunction and resemble the patterns of neuroinflammation that have been described in HIV infection...
March 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28137224/sulfated-glycans-in-hiv-infection-and-therapy
#11
Vitor H Pomin, Francisco F Bezerra, Paulo A G Soares
The human immunodeficiency virus (HIV) is the infectious agent causative of the acquired immune deficiency syndrome (AIDS). The number of HIV-infected people in the globe is incredibly large. Contrary to the big contamination rates, the incidence recently reported to AIDS-related deaths are fairly lower, less than 5 % of the total infected population. The reduced rates of the AIDS-associated deaths rely primarily on the growing availability, variety and efficiency of the antiretroviral treatments. During the initial molecular events of the HIV infectivity, the glycoprotein gp120 on the HIV envelop must interact with CD4 and heparan sulfate (HS) proteoglycans on the surface of the host cells in order to enable HIV attachment, fusion and entry into these cells...
January 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28133805/evolution-of-b-cell-analysis-and-env-trimer-redesign
#12
REVIEW
Gunilla B Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T Wyatt
HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133801/anti-retroviral-antibody-fc%C3%AE-r-mediated-effector-functions
#13
REVIEW
Stylianos Bournazos, Jeffrey V Ravetch
The antiviral activity of antibodies reflects the bifunctional properties of these molecules. While the Fab domains mediate highly specific antigenic recognition to block virus entry, the Fc domain interacts with diverse types of Fcγ receptors (FcγRs) expressed on the surface of effector leukocytes to induce the activation of distinct immunomodulatory pathways. Fc-FcγR interactions are tightly regulated to control IgG-mediated inflammation and immunity and are largely determined by the structural heterogeneity of the IgG Fc domain, stemming from differences in the primary amino acid sequence of the various subclasses, as well as the structure and composition of the Fc-associated N-linked glycan...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133717/dopamine-increases-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-implications-for-substance-abuse-and-hiv-neuropathogenesis
#14
Tina M Calderon, Dionna W Williams, Lillie Lopez, Eliseo A Eugenin, Laura Cheney, Peter J Gaskill, Mike Veenstra, Kathryn Anastos, Susan Morgello, Joan W Berman
In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14(+)CD16(+) monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14(+)CD16(+) monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND...
January 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28130445/interferon-inducible-ly6e-protein-promotes-hiv-1-infection
#15
Jingyou Yu, Chen Liang, Shan-Lu Liu
LY6E is a glycosylphosphatidylinositol (GPI)-anchored, interferon (IFN)-inducible protein that regulates T lymphocytes proliferation, differentiation and development. Single nucleotide polymorphism rs2572886 in LY6-family protein locus has been shown to associate with accelerated progression to AIDS. In this study, we showed that LY6E promotes HIV-1 infection by enhancing viral entry and gene expression. Knockdown of LY6E in human PBMCs, SupT1, and THP-1 cells diminishes HIV-1 replication. Virion-cell and cell-cell fusion experiments revealed that LY6E promotes membrane fusion of the viral entry step...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28125699/uptake-and-acceptability-of-oral-hiv-self-testing-among-community-pharmacy-clients-in-kenya-a-feasibility-study
#16
Peter M Mugo, Murugi Micheni, Jimmy Shangala, Mohamed H Hussein, Susan M Graham, Tobias F Rinke de Wit, Eduard J Sanders
BACKGROUND: While HIV testing and counselling is a key entry point for treatment as prevention, over half of HIV-infected adults in Kenya are unaware they are infected. Offering HIV self-testing (HST) at community pharmacies may enhance detection of undiagnosed infections. We assessed the feasibility of pharmacy-based HST in Coastal Kenya. METHODS: Staff at five pharmacies, supported by on-site research assistants, recruited adult clients (≥18 years) seeking services indicative of HIV risk...
2017: PloS One
https://www.readbyqxmd.com/read/28125233/depth-dependent-membrane-ordering-by-hemagglutinin-fusion-peptide-promotes-fusion
#17
Hirak Chakraborty, Barry R Lentz, Mamata Kombrabail, G Krishnamoorthy, Amitabha Chattopadhyay
Membrane fusion, one of the most fundamental processes in life, occurs when two separate lipid membranes merge into a single continuous bilayer. Membrane fusion is essential for the entry of lipid-sheathed viruses such as influenza and HIV. Influenza virus is internalized via receptor-mediated endocytosis and then fuses with the endosomal membrane at low pH. Hemagglutinin, a glycoprotein found on the surface of influenza virus, is responsible for the fusion of the viral sheath with the endosomal membrane. The ∼20 amino acid long N-terminus of hemagglutinin, known as the fusion peptide, plays a crucial role in the viral fusion process...
February 9, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28124959/-prevalence-of-human-leukocyte-antigen-hla-b-57-01-in-hiv-infected-patients
#18
Aydın Deveci, Ahmet Yılmaz Çoban, Belma Durupınar
Deaths related with human immunodeficiency virus (HIV) infections have been decreased by the introduction of combined anti-retroviral therapy (ART) into the clinical practice. Combined ART usually consists of two nucleoside/nucleotide analogs reverse transcriptase inhibitors (NRTI) that is called backbone and a third drug that belongs to either non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), integrase strand transfer inhibitors (INSTI) or entry inhibitors. During abacavir therapy which is a member of NRTI, hypersensitivity reactions can occur approximately 4-9% of the patients that lead difficulties for the management of HIV infections...
October 2016: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28121714/hepatitis-delta-and-hiv-infection
#19
Vincent Soriano, Kenneth E Sherman, Pablo Barreiro
Viral liver diseases are frequent co-morbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Whereas cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union and North America, sexual contact has replaced injection drug use has major transmission route for HDV in HIV-positive persons...
January 24, 2017: AIDS
https://www.readbyqxmd.com/read/28121710/improved-quality-of-life-with-immediate-initiation-of-antiretroviral-therapy-in-the-strategic-timing-of-antiretroviral-therapy-trial
#20
Alan R Lifson, Birgit Grund, Edward M Gardner, Richard Kaplan, Eileen Denning, Nicole Engen, Catherine L Carey, Fabian Chen, Sounkalo Dao, Eric Florence, Jesus Sanz, Sean Emery
OBJECTIVE: To determine if immediate compared to deferred initiation of antiretroviral therapy (ART) in healthy persons living with HIV (PLWH) had a more favorable impact on health-related quality of life (QOL), or self-assessed physical, mental and overall health status. DESIGN: QOL was measured in START (Strategic Timing of Antiretroviral Therapy), which randomized healthy ART naive PLWH with >500 CD4+ cells/μl from 35 countries to immediate versus deferred ART...
January 24, 2017: AIDS
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