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Hiv entry

Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I Bukrinsky, Paul J Brindley
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein...
October 2016: PLoS Pathogens
Maria Prokofjeva, Vladimir Tsvetkov, Dmitry Basmanov, Anna Varizhuk, Maria Lagarkova, Igor Smirnov, Kirill Prusakov, Dmitry Klinov, Vladimir Prassolov, Galina Pozmogova, Sergey N Mikhailov
New natural and chemically modified DNA aptamers that inhibit HIV-1 activity at submicromolar concentrations (presumably via preventing viral entry into target cells) are reported. The new DNA aptamers were developed based on known intramolecular G-quadruplexes (G4s) that were functionally unrelated to HIV inhibition [the thrombin-binding aptamer and the fragment of the human oncogene promoter (Bcl2)]. The majority of previously described DNA inhibitors of HIV infection adopt intermolecular structures, and thus their folding variability represents an obvious disadvantage...
October 20, 2016: Nucleic Acid Therapeutics
Colin M Venner, Immaculate Nankya, Fred Kyeyune, Korey Demers, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Barbara Van Der Pol, Peter Mugyenyi, Robert A Salata, Charles S Morrison, Eric J Arts
INTRODUCTION: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes. METHODS: Newly HIV infected Ugandan and Zimbabwean women (N=303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5years. RESULTS: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P<0...
October 12, 2016: EBioMedicine
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Hinojal Zazo, Clara I Colino, Klaudia T Warzecha, Mareike Hoss, Uwe Gbureck, Christian Trautwein, Frank Tacke, José M Lanao, Matthias Bartneck
The human immunodeficiency virus (HIV) continues to be a global pandemic and there is an urgent need for innovative treatment. Immune cells represent a major target of virus infection, but are also therapeutic targets. Currently, no antiretroviral therapy targets macrophages, which function as portal of entry and as major long-term deposit of HIV. It has been shown before that human macrophages efficiently internalize gold nanoparticles, a fact which might be used to target them with drug-nanoparticle conjugates...
October 17, 2016: Macromolecular Bioscience
Ming Sun, Yue Li, Huiwen Zheng, Yiming Shao
The recent discoveries of broadly potent neutralizing human monoclonal antibodies represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer and have been proved to provide passive protection against mucosal challenge in humanized mice and macaques. Several neutralizing Abs could protect animals against HIV-1 but are not effective when used in an established infected model for therapy. In order to overcome the limitation of antiviral activities, multiple antibody-engineering technologies have been explored to generate "the better" neutralizing antibodies against HIV-1 since bNAbs attack viral entry by various mechanisms...
2016: Frontiers in Immunology
Huilian Wang, Xi Lu, Xudong Yang, Nan Xu
BACKGROUND: To date, a definite conclusion about efficiency and safety of tenofovir alafenamide for patients with HIV-1 is not available. The aim of the study was to investigate the efficacy and safety of TAF versus TDF in antiretroviral regimens for patients with HIV-1. METHODS: PUBMED, MEDLINE, and EMBASE database were searched in March 2016, with no language restriction, for randomized controlled trials (RCTs). RESULTS: Six RCTs (n = 5888) met entry criteria...
October 2016: Medicine (Baltimore)
Bibek Parajuli, Kriti Acharya, Reina Yu, Brendon Ngo, Adel A Rashad, Cameron F Abrams, Irwin M Chaiken
We recently reported discovery of a recombinant chimera, denoted DAVEI (Dual Acting Virucidal Entry Inhibitor), which is able to selectively cause specific and potent lytic inactivation of both pseudotyped and fully infectious HIV-1 virions. The chimera is composed of the lectin cyanovirin-N (CVN) fused to the 20-residue membrane-proximal external region (MPER) of HIV-1 gp41. Since the Env gp120-binding CVN domain on its own is not lytic, we sought here to determine how the MPER(DAVEI) domain is able to endow the chimera with virolytic activity...
October 12, 2016: Biochemistry
Xia Wang, Sanyi Tang, Xinyu Song, Libin Rong
HIV can infect cells via virus-to-cell infection or cell-to-cell viral transmission. These two infection modes may occur in a synergistic way and facilitate viral spread within an infected individual. In this paper, we developed an HIV latent infection model including both modes of transmission and time delays between viral entry and integration or viral production. We analysed the model by defining the basic reproductive number, showing the existence, positivity and boundedness of the solution, and proving the local and global stability of the infection-free and infected steady states...
October 12, 2016: Journal of Biological Dynamics
Kevin K Ariën, Françoise Baleux, Delphine Desjardins, Françoise Porrot, Yves-Marie Coïc, Johan Michiels, Kawthar Bouchemal, David Bonnaffé, Timothée Bruel, Olivier Schwartz, Roger Le Grand, Guido Vanham, Nathalie Dereuddre-Bosquet, Hugues Lortat-Jacob
The CD4 and the cryptic coreceptor binding sites of the HIV-1 envelope glycoprotein are key to viral attachment and entry. We developed new molecules comprising a CD4 mimetic peptide linked to anionic compounds (mCD4.1-HS12 and mCD4.1-PS1), that block the CD4-gp120 interaction and simultaneously induce the exposure of the cryptic coreceptor binding site, rendering it accessible to HS12- or PS1- mediated inhibition. Using a cynomolgus macaque model of vaginal challenge with SHIV162P3, we report that mCD4.1-PS1, formulated into a hydroxyethyl-cellulose gel provides 83% protection (5/6 animals)...
October 10, 2016: Scientific Reports
Guan-Han Li, Lisa Henderson, Avindra Nath
If we have any hope of achieving a cure for HIV infection, close attention to the cell types capable of getting infected with HIV is necessary. Of these cell types, astrocytes are the most ideal cell type for the formation of such a reservoir. These are long-lived cells with a very low turnover rate and are found in the brain and the gastrointestinal tract. Although astrocytes are evidently resistant to infection of cell-free HIV in vitro, these cells are efficiently infected via cell-to-cell contact by which immature HIV virions bud off lymphocytes and have ability directly bind to CXCR4 triggering the process of fusion in the absence of CD4...
October 6, 2016: Current HIV Research
Francesca Curreli, Dmitry S Belov, Ranjith R Ramesh, Naisargi Patel, Andrea Altieri, Alexander V Kurkin, Asim K Debnath
Since our first discovery of a CD4-mimic, NBD-556, which targets the Phe43 cavity of HIV-1 gp120, we and other groups made considerable progress in designing new CD4-mimics with viral entry-antagonist property. In our continued effort to make further progress we have synthesized twenty five new analogs based on our earlier reported viral entry antagonist, NBD-11021. These compounds were tested first in HIV-1 Env-pseudovirus based single-cycle infection assay as well as in a multi-cycle infection assay. Four of these new compounds showed much improved antiviral potency as well as cytotoxicity...
September 24, 2016: Bioorganic & Medicinal Chemistry
V Dorsamy, C Vallen, F Haffejee, J Moodley, T Naicker
OBJECTIVE: To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. DESIGN: Cross-sectional immunohistochemical analysis of target receptor expression. SETTING: Laboratory-based study of primigravidae attending a district hospital in South Africa...
October 3, 2016: BJOG: An International Journal of Obstetrics and Gynaecology
Chuncheng Liu, Jessica Mao, Terrence Wong, Weiming Tang, Lai Sze Tso, Songyuan Tang, Ye Zhang, Wei Zhang, Yilu Qin, Zihuang Chen, Wei Ma, Dianming Kang, Haochu Li, Meizhen Liao, Katie Mollan, Michael Hudgens, Barry Bayus, Shujie Huang, Bin Yang, Chongyi Wei, Joseph D Tucker
INTRODUCTION: Crowdsourcing has been used to spur innovation and increase community engagement in public health programmes. Crowdsourcing is the process of giving individual tasks to a large group, often involving open contests and enabled through multisectoral partnerships. Here we describe one crowdsourced video intervention in which a video promoting condom use is produced through an open contest. The aim of this study is to determine whether a crowdsourced intervention is as effective as a social marketing intervention in promoting condom use among high-risk men who have sex with men (MSM) and transgender male-to-female (TG) in China...
October 3, 2016: BMJ Open
Claire Da Silva Santos, Kevin Tartour, Andrea Cimarelli
To better characterize the behavior of HIV-1 capsids we developed EURT, for Entry/Uncoating assay based on core-packaged RNA availability and Translation. EURT is an alternative to Blam-Vpr, but as reporter RNA translation relies on core opening, it can be used to study viral capsids behavior. Our study reveals the existence of two major capsid species, a dead end one in which the viral genome is readily exposed to the cytoplasm and a functional one in which such exposure requires artificial core destabilization...
September 2016: PLoS Pathogens
Barbara Castelnuovo, Rachel Musomba, Joseph Musaazi, Agnes N Kiragga
In resource-limited settings, a number of patients do not receive continuous HIV care. In this analysis, we compared outcomes in patients who entered care by different modality of entry. This was a retrospective analysis of all patients started on antiretroviral treatment (ART) at a large urban center in Uganda from 2005 to 2012. Patients were categorized into three groups (1) Front door: started on ART without interruption during follow-up; (2) drop-out side door: restarted on ART after having an interruption >6 months and (3) transfer-in side door: transferred-in after being started on ART somewhere else...
August 15, 2016: AIDS Care
Janan Janine Dietrich, Fatima Laher, Stefanie Hornschuh, Busisiwe Nkala, Lucy Chimoyi, Kennedy Otwombe, Angela Kaida, Glenda Elisabeth Gray, Cari Miller
BACKGROUND: Internet access via mobile phones and computers facilitates interaction and potential health communication among individuals through social networking. Many South African adolescents own mobile phones and can access social networks via apps. OBJECTIVE: We investigated sociodemographic factors and HIV risk behaviors of adolescent social networking users in Soweto, South Africa. METHODS: We conducted an interviewer-administered, cross-sectional survey of adolescents aged 14-19 years...
2016: JMIR Public Health and Surveillance
W Huang, M Calvo, T Pheby, D L H Bennett, A S C Rice
HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours...
September 23, 2016: Pain
Nerea Huarte, Pablo Carravilla, Antonio Cruz, Maier Lorizate, Jon A Nieto-Garai, Hans-Georg Kräusslich, Jesús Pérez-Gil, Jose Requejo-Isidro, José L Nieva
The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes...
September 28, 2016: Scientific Reports
Pranab K Mukherjee, Huichao Chen, Lauren L Patton, Scott Evans, Anthony Lee, Johnstone Kumwenda, James Hakim, Gaerolwe Masheto, Frederick Sawe, Mai T Pho, Kenneth A Freedberg, Caroline H Shiboski, Mahmoud A Ghannoum, Robert A Salata
OBJECTIVE: Compare the safety and efficacy of topical gentian violet (GV) to that of nystatin oral suspension (NYS) for the treatment of oropharyngeal candidiasis (OC) in HIV-1 infected adults in resource-limited settings. DESIGN: Multicenter, open-label, evaluator-blinded, randomized clinical trial at 8 international sites, within the AIDS Clinical Trials Group. STUDY PARTICIPANTS AND INTERVENTION: Adult HIV-infected participants with OC, stratified by CD4 cell counts and antiretroviral therapy status at study entry, were randomized to receive either GV (0...
September 24, 2016: AIDS
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