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https://www.readbyqxmd.com/read/29778602/structure-guided-combinatorial-engineering-facilitates-affinity-and-specificity-optimization-of-anti-cd81-antibodies
#1
Bryce Nelson, Jarrett Adams, Andreas Kuglstatter, Zhijian Li, Seth F Harris, Yang Liu, Sandya Bohini, Han Ma, Klaus Klumpp, Junjun Gao, Sachdev S Sidhu
Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block Hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop (LEL) in order to guide affinity maturation of two distinct antibodies by phage display...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29778137/deciphering-natural-control-of-hiv-1-a-valuable-strategy-to-achieve-antiretroviral-therapy-termination
#2
REVIEW
Hamza Loucif, Steven Gouard, Xavier Dagenais-Lussier, Armstrong Murira, Simona Stäger, Cécile Tremblay, Julien Van Grevenynghe
Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance...
April 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29777749/burden-of-liver-disease-in-europe-epidemiology-and-analysis-of-risk-factors-to-identify-prevention-policies
#3
REVIEW
Laura Pimpin, Helena Cortez-Pinto, Francesco Negro, Emily Corbould, Jeffrey V Lazarus, Laura Webber, Nick Sheron
BACKGROUND & AIMS: The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. METHODS: As part of the HEPAHEALTH project, commissioned by EASL, we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the WHO European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections...
May 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29777191/eradication-of-hepatitis-c-virus-is-associated-with-the-attenuation-of-steatosis-as-evaluated-using-a-controlled-attenuation-parameter
#4
Kohei Shimizu, Yoko Soroida, Masaya Sato, Hiromi Hikita, Tamaki Kobayashi, Momoe Endo, Mamiko Sato, Hiroaki Gotoh, Tomomi Iwai, Ryosuke Tateishi, Kazuhiko Koike, Yutaka Yatomi, Hitoshi Ikeda
Chronic hepatitis C virus (HCV) infection was shown to cause hepatic steatosis or suppression of serum lipid levels. However, little is known about the changes in hepatic steatosis following HCV eradication. We aimed to evaluate this issue using the controlled attenuation parameter (CAP), which was recently shown to provide a standardized non-invasive measure of hepatic steatosis. We enrolled 70 patients with chronic HCV infections and steatosis (CAP of over 248 dB/m) who had achieved a sustained viral response at 12 weeks after discontinuation of antiviral treatment using direct-acting antivirals (DAA)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775812/virus-entry-and-its-inhibition-to-prevent-and-treat-hepatitis-b-and-hepatitis-d-virus-infections
#5
REVIEW
Thomas Tu, Stephan Urban
While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis...
May 15, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29773081/long-term-familial-mediterranean-fever-remission-on-successful-hepatitis-c-virus-treatment-in-a-patient-not-responding-to-colchicine-a-case-report
#6
Manik Gemilyan, Gagik Hakobyan, Susanna Ananyan
BACKGROUND: Familial Mediterranean fever is an autosomal recessive disorder characterized by periodic febrile attacks of aseptic serositis and/or arthritis. The main treatment is colchicine which prevents attacks in the majority of patients except for a group of colchicine-resistant cases. Chronic hepatitis C is a viral infection causing chronic inflammation of liver tissue (hepatitis) which ultimately progresses to fibrosis and liver cirrhosis with a high chance of hepatocellular carcinoma...
May 18, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29772941/recent-advances-in-the-discovery-and-development-of-tlr-ligands-as-novel-therapeutics-for-chronic-hbv-and-hiv-infections
#7
Keye Du, Jia Liu, Ruth Broering, Xiaoyong Zhang, Dongliang Yang, Ulf Dittmer, Mengji Lu
Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands ...
May 17, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29772748/drug-delivery-strategies-for-antivirals-against-hepatitis-b-virus
#8
REVIEW
Latavia Singh, Sunaina Indermun, Mershen Govender, Pradeep Kumar, Lisa C du Toit, Yahya E Choonara, Viness Pillay
Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles...
May 17, 2018: Viruses
https://www.readbyqxmd.com/read/29772664/the-cholinergic-anti-inflammatory-response-and-the-role-of-macrophages-in-hiv-induced-inflammation
#9
REVIEW
Manuel Delgado-Vélez, José A Lasalde-Dominicci
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772420/the-search-for-biomarkers-of-hepatocellular-carcinoma-and-the-impact-on-patient-outcome
#10
REVIEW
Alyson P Black, Anand S Mehta
Hepatocellular carcinoma (HCC) is the 5th most common cancer, but the 3rd leading cause of cancer death globally with approximately 700,000 fatalities annually. The severity of this cancer arises from its difficulty to detect and treat. The major etiologies of HCC are liver fibrosis or cirrhosis from chronic viral infections, as well as metabolic conditions. Since most cases arise from prior pathologies, biomarker surveillance in high-risk individuals is an essential approach for early detection and improved patient outcome...
May 14, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29769725/mxra8-is-a-receptor-for-multiple-arthritogenic-alphaviruses
#11
Rong Zhang, Arthur S Kim, Julie M Fox, Sharmila Nair, Katherine Basore, William B Klimstra, Rebecca Rimkunas, Rachel H Fong, Hueylie Lin, Subhajit Poddar, James E Crowe, Benjamin J Doranz, Daved H Fremont, Michael S Diamond
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#12
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769442/distinct-biomarker-signatures-in-hiv-acute-infection-associate-with-viral-dynamics-and-reservoir-size
#13
Jeffrey E Teigler, Louise Leyre, Nicolas Chomont, Bonnie Slike, Ningbo Jian, Michael A Eller, Nittaya Phanuphak, Eugène Kroon, Suteeraporn Pinyakorn, Leigh Anne Eller, Merlin L Robb, Jintanat Ananworanich, Nelson L Michael, Hendrik Streeck, Shelly J Krebs
Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769036/estimates-of-state-level-chronic-hepatitis-c-virus-infection-stratified-by-race-and-sex-united-states-2010
#14
Eric W Hall, Eli S Rosenberg, Patrick S Sullivan
BACKGROUND: Hepatitis C virus (HCV) is the most common blood-borne viral infection in the United States. Previously, we used data from the National Health and Nutrition Examination Survey (NHANES) and mortality data from the National Vital Statistics System (NVSS) to estimate the prevalence of HCV antibodies (anti-HCV) and HCV RNA among all U.S. states. However, demographic differences in HCV burden at the state-level have not been systematically described. This analysis quantified the HCV burden stratified by sex and race (and associated disparities) for each U...
May 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29768691/detection-of-hepatitis-b-virus-dna-among-chronic-and-potential-occult-hbv-patients-in-resource-limited-settings-by-loop-mediated-isothermal-amplification-assay
#15
Arifa Akram, S M Rashedul Islam, Saif Ullah Munshi, Shahina Tabassum
Transmission of Hepatitis B Virus (HBV) usually occurs due to the transfusion of blood or blood products from chronic HBV (CHB) or occult HBV infected (OBI) patients. Besides serological tests e.g. HBsAg and anti-HBc (total), detection of HBV-DNA is necessary for the diagnosis of OBI patients. Different nucleic acid tests (NATs) including real-time-Polymerase Chain Reaction (qPCR) are used for the detect HBV-DNA. The NATs are expensive and require technical expertise which are barriers to introducing them in resource-limited settings...
May 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29768546/first-wave-protease-inhibitors-for-hepatitis-c-genotype-1-treatment-a-real-life-experience-in-brazilian-patients
#16
Silvana Gama Florencio Chachá, João Paulo Vilela Rodrigues, Roberta Chaves Araújo, Leonardo Régis Leira Pereira, Márcia Guimarães Villanova, Fernanda Fernandes Souza, Rodrigo de Carvalho Santana, Ana de Lourdes Candolo Martinelli
INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center...
March 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29768211/long-term-persistence-of-exhausted-cd8-t-cells-in-chronic-infection-is-regulated-by-microrna-155
#17
Erietta Stelekati, Zeyu Chen, Sasikanth Manne, Makoto Kurachi, Mohammed-Alkhatim Ali, Keith Lewy, Zhangying Cai, Kito Nzingha, Laura M McLane, Jennifer L Hope, Adam J Fike, Peter D Katsikis, E John Wherry
Persistent viral infections and tumors drive development of exhausted T (TEX ) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over time, leading to loss of pathogen or cancer containment. We identified microRNA (miR)-155 as a key regulator of sustained TEX cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency of miR-155 ablated CD8 T cell responses during chronic infection. Conversely, enhanced miR-155 expression promoted expansion and long-term persistence of TEX cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768180/dietary-fiber-confers-protection-against-flu-by-shaping-ly6c-patrolling-monocyte-hematopoiesis-and-cd8-t-cell-metabolism
#18
Aurélien Trompette, Eva S Gollwitzer, Céline Pattaroni, Isabel C Lopez-Mejia, Erika Riva, Julie Pernot, Niki Ubags, Lluis Fajas, Laurent P Nicod, Benjamin J Marsland
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c- patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29766018/usefulness-of-simultaneous-screening-for-hiv-and-hepatitis-c-specific-antibodies-and-hepatitis-b-surface-antigen-by-capillary-based-multiplex-immunochromatographic-rapid-test-to-strengthen-prevention-strategies-and-linkage-to-care-in-childbearing-aged-women
#19
Ralph-Sydney Mboumba Bouassa, Zita Aleyo Nodjikouambaye, Damtheou Sadjoli, Ali Mahamat Moussa, Chatte Adawaye, Donato Koyalta, Laurent Bélec
Childbearing-aged women (n = 266) attending a gynecological clinic in Chad were subjected to multiplex immunochromatographic rapid test for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). Ten (3.7%) and 8 (3.0%) were seropositive for HIV and HCV, respectively, and 20 (7.5%) for HBV surface antigen, allowing diagnosis of chronic viral infections in 1 of 7 (14.3%) women.
May 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29765238/higher-baseline-viral-diversity-correlates-with-lower-hbsag-decline-following-pegylated-interferon-alpha-therapy-in-patients-with-hbeag-positive-chronic-hepatitis-b
#20
Hu Li, Li Zhang, Hong Ren, Peng Hu
Background: Viral diversity seems to predict treatment outcomes in certain viral infections. The aim of this study was to evaluate the association between baseline intra-patient viral diversity and hepatitis B surface antigen (HBsAg) decline following PEGylated interferon-alpha (Peg-IFN-α) therapy. Patients and methods: Twenty-six HBeAg-positive patients who were treated with Peg-IFN-α were enrolled. Nested polymerase chain reaction (PCR), cloning, and sequencing of the hepatitis B virus S gene were performed on baseline samples, and normalized Shannon entropy (Sn) was calculated as a measure of small hepatitis B surface protein (SHBs) diversity...
2018: Infection and Drug Resistance
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