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https://www.readbyqxmd.com/read/28630320/%C3%AE-20-ifitm2-differentially-restricts-x4-and-r5-hiv-1
#1
Wan-Lin Wu, Christopher Robert Grotefend, Ming-Ting Tsai, Yi-Ling Wang, Vladimir Radic, Hyungjin Eoh, I-Chueh Huang
CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4(+) T cells and in monocytes...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28624214/further-characterization-of-the-bifunctional-hiv-entry-inhibitor-scd4-fit45
#2
Alexander Falkenhagen, Sadhna Joshi
HIV entry into target cells is a highly sequential and time-sensitive process. In recent years, potent HIV Env-targeting antibodies, such as VRC01, have been identified. However, antibodies bind only to a single epitope, and mutations that confer resistance to antibody-mediated inhibition of HIV entry have been detected. In contrast, HIV cannot escape from binding to soluble CD4 (sCD4) without a fitness disadvantage. sCD4 has the unique ability to induce conformational changes within the HIV envelope glycoproteins (Env) that allow fusion inhibitors to bind...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623807/hiv-tat-excites-d1-receptor-like-expressing-neurons-from-rat-nucleus-accumbens
#3
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca(2+) homeostasis of NAcc neurons...
June 8, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28623185/a-web-based-data-collection-platform-for-multisite-randomized-behavioral-intervention-trials-development-key-software-features-and-results-of-a-user-survey
#4
Riddhi A Modi, Michael J Mugavero, Rivet K Amico, Jeanne Keruly, Evelyn Byrd Quinlivan, Heidi M Crane, Alfredo Guzman, Anne Zinski, Solange Montue, Katya Roytburd, Anna Church, James H Willig
BACKGROUND: Meticulous tracking of study data must begin early in the study recruitment phase and must account for regulatory compliance, minimize missing data, and provide high information integrity and/or reduction of errors. In behavioral intervention trials, participants typically complete several study procedures at different time points. Among HIV-infected patients, behavioral interventions can favorably affect health outcomes. In order to empower newly diagnosed HIV positive individuals to learn skills to enhance retention in HIV care, we developed the behavioral health intervention Integrating ENGagement and Adherence Goals upon Entry (iENGAGE) funded by the National Institute of Allergy and Infectious Diseases (NIAID), where we deployed an in-clinic behavioral health intervention in 4 urban HIV outpatient clinics in the United States...
June 16, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28606392/hiv-and-hepatitis-c-treatment-uptake-among-people-who-use-drugs-participating-in-the-amsterdam-cohort-studies-1985-2015
#5
Daniëla K van Santen, Jannie J van der Helm, Karen Lindenburg, Maarten Schim van der Loeff, Maria Prins
BACKGROUND: HIV-positive people who use drugs (PWUD) start antiretroviral therapy (ART) later than other risk groups, and among HCV-positive PWUD, HCV treatment uptake is low. Nowadays, HCV direct-acting antivirals (DAAs) are available and reimbursed in the Netherlands (since 2014). The Amsterdam Cohort Studies (ACS), initiated in 1985, provides us the opportunity to describe temporal trends in ART and HCV-treatment uptake among PWUD through 2015. METHODS: We analyzed data from PWUD participating in the ACS between 1985 and 2015...
June 9, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28605171/human-immunodeficiency-virus-care-cascade-among-sub-populations-in-rakai-uganda-an-observational-study
#6
Veena G Billioux, Larry W Chang, Steven J Reynolds, Gertrude Nakigozi, Joseph Ssekasanvu, Mary K Grabowski, Robert Ssekubugu, Fred Nalugoda, Godfrey Kigozi, Joseph Kagaayi, David Serwadda, Ronald H Gray, Maria J Wawer
INTRODUCTION: To assess progress towards the UNAIDS 90-90-90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. METHODS: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ(2) test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART)...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28604824/decline-in-cd4-t-lymphocytes-with-monotherapy-bridging-strategy-for-non-adherent-adolescents-living-with-hiv-infection-results-of-the-impaact-p1094-randomized-trial
#7
Allison L Agwu, Meredith G Warshaw, Elizabeth J McFarland, George K Siberry, Ann J Melvin, Andrew A Wiznia, Lee Fairlie, Sandra Boyd, Paul Harding, Hans M L Spiegel, Elaine J Abrams, Vincent J Carey
INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs...
2017: PloS One
https://www.readbyqxmd.com/read/28596938/genome-edited-t-cell-therapies
#8
REVIEW
Juliette M K M Delhove, Waseem Qasim
PURPOSE OF REVIEW: Alternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28592540/covalent-linkage-of-hiv-1-trimers-to-synthetic-liposomes-elicits-improved-b-cell-and-antibody-responses
#9
Shridhar Bale, Geraldine Goebrecht, Armando Stano, Richard Wilson, Takayuki Ota, Karen Tran, Jidnyasa Ingale, Michael B Zwick, Richard T Wyatt
We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimer via their C-terminal poly-histidine tails to nickel-lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remains over the potentially longer term in vivo instability of non-covalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the poly-histidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28584151/discovery-and-characterization-of-a-novel-cd4-binding-adnectin-with-potent-anti-hiv-activity
#10
David Wensel, Yongnian Sun, Zhufang Li, Sharon Zhang, Caryn Picarillo, Thomas McDonagh, David Fabrizio, Mark Cockett, Mark Krystal, Jonathan Davis
A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. This inhibitor binds to human CD4 with high affinity (3.9 nM) and inhibits viral entry at a step post-CD4 engagement and preceding membrane fusion. The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display, then further optimized for improved anti-viral and physical properties. The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad spectrum activity...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28578865/initiating-hcv-treatment-with-direct-acting-agents-in-opioid-agonist-treatment-when-to-start-for-people-co-infected-with-hiv
#11
Dimitra Panagiotoglou, Emanuel Krebs, Jeong Eun Min, Michelle Olding, Keith Ahamad, Lianping Ti, Julio S G Montaner, Bohdan Nosyk
BACKGROUND: Direct acting antivirals (DAA) raise the possibility of eliminating Hepatitis C virus (HCV) among people who inject drugs (PWID). However, concerns regarding treatment retention and reinfection challenge implementation efforts. Opioid agonist treatment (OAT) provides an opportunity to engage HCV-positive PWID into DAA-based treatment. Our objective was to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings, assuming continuous OAT retention for at least twelve weeks is necessary to complete the DAA treatment course...
June 1, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28575798/design-and-computational-support-for-the-binding-stability-of-a-new-ccr5-cxcr4-dual-tropic-inhibitor-computational-design-of-a-ccr5-cxcr4-drug
#12
Cooper A Taylor, Bill R Miller, Carol A Parish
The human immunodeficiency virus (HIV) infects healthy human cells by binding to the glycoprotein cluster of differentiation 4 receptors on the surface of helper T-cells, along with either of two chemokine receptors, CC chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Recently, a pyrazolo-piperdine ligand was synthesized and the corresponding biological data showed good binding to both chemokine receptors, effectively blocking HIV-1 entry. Here, we exhaustively assess the atomistic binding interactions of this compound with both CCR5 and CXCR4, and we find that binding is driven by π-stacking interactions between aromatic rings on the ligand and receptor residues, as well as electrostatic interactions involving the protonated piperidine nitrogen...
February 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#13
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28560901/new-faces-of-hiv-infection-age-race-and-timing-of-entry-into-hiv-care-in-the-southeastern-united-states
#14
Peter F Rebeiro, Kelsey S Ivey, Kaylin S Craig, Todd Hulgan, Moises A Huaman, Robertson Nash, Stephen Raffanti, Kehinde A Equakun, Anna K Person
Among younger men who have sex with men (MSM), the incidence of HIV is rising nationally. Of the 281 persons who entered into care at a large HIV clinic in the southeastern United States in 2010 to 2012, 78 (27.8%) were <25 years old at the time of diagnosis. Those in the younger group were more likely than those aged ≥25 to be black (59.0% versus 37.4%), MSM (78.2% versus 55.2%), and to have a longer median time from diagnosis to entry into care (71 versus 53 days; P < .05 each). In adjusted survival analysis, persons of black race were less likely to enter care after diagnosis than those of nonblack race (hazard ratio = 0...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28558972/structure-based-identification-of-inhibitors-targeting-obstruction-of-the-hivgp41-n-heptad-repeat-trimer
#15
T Dwight McGee, Hyun Ah Yi, William J Allen, Amy Jacobs, Robert C Rizzo
The viral protein HIVgp41 is an attractive and validated drug target that proceeds through a sequence of conformational changes crucial for membrane fusion, which facilitates viral entry. Prior work has identified inhibitors that interfere with the formation of a required six-helix bundle, composed of trimeric C-heptad (CHR) and N-heptad (NHR) repeat elements, through blocking association of an outer CHR helix or obstructing formation of the inner NHR trimer itself. In this work, we employed similarity-based scoring to identify and experimentally characterize 113 compounds, related to 2 small-molecule inhibitors recently reported by Allen et al...
May 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28542260/hookworm-infection-is-associated-with-decreased-cd4-t-cell-counts-in-hiv-infected-adult-ugandans
#16
Bozena M Morawski, Miya Yunus, Emmanuel Kerukadho, Grace Turyasingura, Logose Barbra, Andrew Mijumbi Ojok, Andrew R DiNardo, Stefanie Sowinski, David R Boulware, Rojelio Mejia
Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28539445/structure-of-simian-immunodeficiency-virus-envelope-spikes-bound-with-cd4-and-monoclonal-antibody-36d5
#17
Guiqing Hu, Jun Liu, Kenneth H Roux, Kenneth A Taylor
The HIV-1/SIV envelope spike (Env) mediates the viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the co-receptor binding site and is a target for neutralizing antibodies. We have used cryoelectron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody 36D5 to gp120 of the SIV Env. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest the antibody exerts its neutralization effect by blocking the co-receptor binding site...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538165/the-complexity-in-herpesvirus-entry
#18
REVIEW
Karthik Sathiyamoorthy, Jia Chen, Richard Longnecker, Theodore S Jardetzky
Enveloped viruses have evolved diverse transmembrane proteins and protein complexes to enable host cell entry by regulating and activating membrane fusion in a target cell-specific manner. In general terms, the entry process requires a receptor binding step, an activation step and a membrane fusion step, which can be encoded within a single viral protein or distributed among multiple viral proteins. HIV and influenza virus, for example, encode all of these functions in a single trimeric glycoprotein, HIV env or influenza virus hemagglutinin (HA)...
May 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28537061/dolutegravir-lamivudine-as-initial-therapy-in-hiv-1-infected-arv-naive-patients-48-week-results-of-the-paddle-pilot-antiretroviral-design-with-dolutegravir-lamivudine-study
#19
Pedro Cahn, María José Rolón, María Inés Figueroa, Ana Gun, Patricia Patterson, Omar Sued
INTRODUCTION: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. METHODS: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg...
May 9, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28534889/hiv-1-infection-in-persons-homozygous-for-ccr5-%C3%AE-32-allele-the-next-case-and-the-review
#20
Joanna Smoleń-Dzirba, Magdalena Rosińska, Janusz Janiec, Marek Beniowski, Mariusz Cycoń, Jolanta Bratosiewicz-Wąsik, Tomasz J Wąsik
CC-chemokine receptor 5 serves as the coreceptor for the HIV-1 R5 strains, which are responsible for the majority of HIV transmissions. A deletion of 32 nucleotides in the gene encoding this receptor (termed CCR5-Δ32) leads to the suppression of CC-chemokine receptor 5 presentation at the cell surface, thus impeding process of HIV entry into the cell. Individuals homozygous for the CCR5-Δ32 allele are resistant to infection with HIV-1 R5 strains, and are extremely rare among HIV-1-infected individuals. We have described a case of person homozygous for CCR5-Δ32, who was infected with subtype B HIV-1...
May 23, 2017: AIDS Reviews
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