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https://www.readbyqxmd.com/read/29773895/crispr-cas9-system-targeting-regulatory-genes-of-hiv-1-inhibits-viral-replication-in-infected-t-cell-cultures
#1
Youdiil Ophinni, Mari Inoue, Tomohiro Kotaki, Masanori Kameoka
The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genes tat and rev with guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29771784/zika-virus-exposure-in-an-hiv-infected-cohort-in-ghana
#2
K E Sherman, S D Rouster, L X Kong, T M Shata, T Archampong, A Kwara, M T Aliota, J T Blackard
OBJECTIVE: To determine the prevalence and epidemiologic associations of Zika Virus (ZIKV) in HIV-infected patients in Ghana, West Africa. METHODS: We examined the seroprevalence of ZIKV in HIV/HBV co-infected persons in Ghana from sera samples collected from 2012 to 2014 using ELISA assays and plaque reduction neutralization tests (PRNT). RESULTS: Overall, ZIKV antibody was detected in 12.9% of 236 tested samples, though the true estimate of exposure is probably less due cross-reactions with other related viruses...
April 27, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29770136/cd3%C3%AE%C2%B5-expression-defines-functionally-distinct-subsets-of-v%C3%AE-1-t-cells-in-patients-with-human-immunodeficiency-virus-infection
#3
Pádraic J Dunne, Christina O Maher, Michael Freeley, Katie Dunne, Andreea Petrasca, Judy Orikiiriza, Margaret R Dunne, Derval Reidy, Siobhan O'Dea, Aisling Loy, Jim Woo, Aideen Long, Thomas R Rogers, Fiona Mulcahy, Derek G Doherty
Human γδ T cells expressing the Vδ1 T cell receptor (TCR) recognize self and microbial antigens and stress-inducible molecules in a major histocompatibility complex-unrestricted manner and are an important source of innate interleukin (IL)-17. Vδ1 T cells are expanded in the circulation and intestines of patients with human immunodeficiency virus (HIV) infection. In this study, we show that patients with HIV have elevated frequencies, but not absolute numbers, of circulating Vδ1 T cells compared to control subjects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769351/protein-phosphatase-1%C3%AE-interacts-with-venezuelan-equine-encephalitis-virus-capsid-protein-and-regulates-viral-replication-through-modulation-of-capsid-phosphorylation
#4
Brian D Carey, Tatiana Ammosova, Chelsea Pinkham, Xionghao Lin, Weidong Zhou, Lance A Liotta, Sergei Nekhai, Kylene Kehn-Hall
Protein Phosphatase 1 (PP1) is a serine/threonine phosphatase which has been implicated in the regulation of a number of viruses including HIV-1, Ebolavirus and Rift Valley fever virus. Catalytic subunits of PP1 (PP1α, PP1β, or PP1γ) interact with a host of regulatory subunits and target a wide variety of cellular substrates through a combination of short binding motifs, including an RVxF motif present in the majority of PP1 regulatory subunits. Targeting the RVxF interacting site on PP1 with the small molecule, 1E7-03 inhibits HIV-1, Ebolavirus, and Rift Valley fever virus replication...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#5
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29767965/bifunctional-chimera-that-coordinately-targets-human-immunodeficiency-virus-1-hiv-1-envelope-gp120-and-host-cell-ccr5-co-receptor-at-the-virus-cell-interface
#6
Adel A Rashad, Li-Rui Song, Andrew P Holmes, Kriti Acharya, Shiyu Zhang, Zhi-Long Wang, Ebony Gary, Xin Xie, Vanessa Pirrone, Michele A Kutzler, Ya-Qiu Long, Irwin Chaiken
To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of HIV-1 Envelope (Env) gp120 and host cell co-receptor (CoR) proteins can be covalently joined into bifunctional synergistic combinations that will improve antiviral. A synthetic protocol was established to covalently combine a CCR5 small molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components, and at the same time exhibited low to sub-nanomolar potencies, in inhibiting cell infection by different pseudoviruses, that were substantially greater than those of a non-covalent mixture of individual components...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767543/efficacy-of-single-tablet-darunavir-cobicistat-emtricitabine-and-tenofovir-alafenamide-in-the-treatment-of-hiv-1
#7
Eugènia Negredo, Bonaventura Clotet
HIV eradication is not feasible and lifelong treatment is warranted to manage HIV infection. In this scenario, the advent of single-tablet, once-daily, fixed-dose co-formulations is important for reducing pill burden and maximize long-term drug adherence. Cobicistat-boosted darunavir along with emtricitabine and tenofovir alafenamide co-formulation (DRV/c/FTC/TAF or the trade name Symtuza®) is the first marketed protease inhibitor-based fixed-dose combination regimen for the treatment of HIV infection. It was approved in late 2017 by the European Medical Agency both for naïve patients and treatment-experienced patients with viral suppression...
May 16, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29766745/incidence-of-acute-kidney-injury-in-patients-co-infected-with-hiv-and-hepatitis-c-virus-receiving-tenofovir-disoproxil-fumarate-and-ledipasvir-sofosbuvir-in-a-real-world-urban-ryan-white-clinic
#8
Jessica L Michal, Saira Rab, Manish Patel, Alison Kyle, Lesley Miller, Kirk A Easley, Aley Kalapila
Background Ledipasvir/sofosbuvir (LDV/SOF), an antiviral treatment for hepatitis C virus (HCV), and tenofovir disoproxil fumarate (TDF), an antiretroviral for treating human immunodeficiency virus (HIV), may be co-administered in patients co-infected with these viruses. A drug interaction between LDV and TDF could increase TDF-associated nephrotoxicity rates; however, there is minimal clinical evidence describing acute kidney injury (AKI) rates in this population. Setting This study was conducted at a Ryan White-funded facility in Atlanta, Georgia, that cares for over 5,000 patients with AIDS...
May 16, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29765256/grazoprevir-elbasvir-for-the-treatment-of-adults-with-chronic-hepatitis-c-a-short-review-on-the-clinical-evidence-and-place-in-therapy
#9
REVIEW
Nimisha Sulejmani, Syed-Mohammed Jafri
Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29760706/complement-opsonized-hiv-1-alters-cross-talk-between-dendritic-cells-and-natural-killer-nk-cells-to-inhibit-nk-killing-and-to-upregulate-pd-1-cxcr3-and-ccr4-on-t-cells
#10
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760133/pharmacokinetics-and-safety-profile-of-artesunate-amodiaquine-co-administered-with-antiretroviral-therapy-in-malaria-uninfected-hiv-positive-malawian-adults
#11
Clifford G Banda, Fraction Dzinjalamala, Mavuto Mukaka, Jane Mallewa, Victor Maiden, Dianne J Terlouw, David G Lalloo, Saye H Khoo, Victor Mwapasa
There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus infected (HIV+) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared area under the concentration-time curve from 0 to 28 days (AUC0-28 days ) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV+ adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29756456/no-time-to-delay-fiebig-stages-and-referral-in-acute-hiv-infection-seattle-primary-infection-program-experience
#12
Joanne Stekler, Kenneth Tapia, Janine Maenza, Claire E Stevens, George Ure, Joshua O'Neal, Aric Lane, James I Mullins, Robert Coombs, Sarah E Holte, Ann Cornwall Collier
INTRODUCTION: There has been increasing recognition of the importance of diagnosing individuals during the earliest stages of HIV infection. MATERIALS AND METHODS: Sera from individuals referred to a primary HIV infection research program were screened using the IgG-sensitive Vironostika HIV-1 Microelisa System, IgG/IgM-sensitive GS HIV-1/HIV-2 Plus O antibody EIA, or Abbott ARCHITECT HIV Ag/Ab Combo assay and confirmed by the Bio-Rad Multispot and Western Blot...
May 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29751762/hiv-latency-reversing-agents-act-through-tat-post-translational-modifications
#13
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian F J Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing...
May 11, 2018: Retrovirology
https://www.readbyqxmd.com/read/29746555/human-herpes-virus-8-in-hiv-1-infected-individuals-receiving-cancer-chemotherapy-and-stem-cell-transplantation
#14
Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Christine D Palmer, Yvonne Robles, Stephanie Jost, Anne S LaCasce, Jeremy Abramson, Ayad Hamdan, Francisco M Marty, Daniel R Kuritzkes, Timothy J Henrich
BACKGROUND: Human Herpes Virus 8 (HHV8) can cause Kaposi's Sarcoma (KS) in immunosuppressed individuals. However, little is known about the association between chemotherapy or hematopoietic stem cell transplantation (HSCT), circulating HHV8 DNA levels, and clinical KS in HIV-1-infected individuals with various malignancies. Therefore, we examined the associations between various malignancies, systemic cancer chemotherapy, T cell phenotypes, and circulating HHV8 DNA in 29 HIV-1-infected participants with concomitant KS or other cancer diagnoses...
2018: PloS One
https://www.readbyqxmd.com/read/29746296/pd-1-contributes-to-the-establishment-and-maintenance-of-hiv-1-latency
#15
Vanessa A Evans, Renée M Van Der Sluis, Ajantha Solomon, Ashanti Dantanarayana, Catriona McNeil, Roger Garsia, Sarah Palmer, Rémi Fromentin, Nicolas Chomont, Rafick-Pierre Sékaly, Paul U Cameron, Sharon R Lewin
OBJECTIVE: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T-cells expressing immune checkpoint molecules (ICs), in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo. METHODS: HIV latency was established in vitro following co-culture of resting CD4 T-cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1 and PD-1 non-proliferating CD4 memory T-cells...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29744126/htlv-1-atll-refractory-hypercalcaemia-and-hiv-1-co-infection
#16
Abdullah E Laher, Feroza Motara, Muhammed Moolla, Osman Ebrahim
Adult T-cell lymphoma/leukemia (ATLL) is a rare tumour of T-lymphocytes that is associated with human T-lymphotrophic virus type 1 (HTLV-1) infection as well as severe/refractory hypercalcaemia. Human immunodefficiency virus type 1 (HIV-1) infected individuals are at increased risk of acquiring co-infection with HTLV-1. We present the case of a 37 -year -old HIV-1 positive and antiretroviral therapy naive woman who was admitted to the ICU with delirium, a generalised maculopapular rash, severe hypercalcaemia of 4...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29741291/epidemiological-characteristics-and-associated-factors-of-acute-hepatitis-a-outbreak-among-hiv-coinfected-men-who-have-sex-with-men-in-taiwan-june-2015-december-2016
#17
Chien-Yu Cheng, Hao-Hsin Wu, Huachun Zou, Yi-Chun Lo
In Taiwan, an outbreak of acute hepatitis A (AHA) infection has been identified since June 2015. Approximately half of the cases occurred in HIV-infected men who have sex with men (MSM). We used the Taiwan Centers for Disease Control (TCDC)-operated National Disease Surveillance Systems (NDSS) to identify the incidence of AHA during 2011-2016. Between June 2015 and December 2016, a total of 1,268 AHA cases were documented, and 601 cases (47.4%) were co-infected with HIV; the majority of whom were MSM (98.4%)...
May 9, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29739341/hbv-and-hiv-viral-load-but-not-microbial-translocation-or-immune-activation-are-associated-with-liver-fibrosis-among-patients-in-south-africa
#18
Tongai Gibson Maponga, Monique I Andersson, Christoffel J van Rensburg, Joop E Arends, Jantjie Taljaard, Wolfgang Preiser, Richard H Glashoff
BACKGROUND: Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection. METHODS: We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa...
May 8, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29737223/cannabinoids-and-reduced-risk-of-hepatic-steatosis-in-hiv-hcv-co-infection-paving-the-way-for-future-clinical-research
#19
Fabienne Marcellin, Hélène Fontaine, Lawrence Serfaty, Philippe Sogni, Maria Patrizia Carrieri
No abstract text is available yet for this article.
May 8, 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29733983/evolutionary-dynamics-of-hepatitis-c-virus-in-a-chronic-hiv-co-infected-patient-and-its-correlation-with-the-immune-status
#20
Andrés Carlos Alberto Culasso, María Cecilia Monzani, Patricia Baré, Rodolfo Hector Campos
The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions...
May 4, 2018: Infection, Genetics and Evolution
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