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https://read.qxmd.com/read/30781904/immune-exhaustion-past-lessons-and-new-insights-from-lymphocytic-choriomeningitis-virus
#1
REVIEW
Shannon M Kahan, Allan J Zajac
Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental for identifying T cell exhaustion and this system has been invaluable for uncovering the complexity, regulators, and consequences of this state. These findings have been directly relevant for understanding why ineffective T cell responses commonly arise during many chronic infections including HIV and HCV, as well as during tumor outgrowth...
February 13, 2019: Viruses
https://read.qxmd.com/read/30776394/high-cd8-t-cell-percentage-and-hcv-replication-control-are-common-features-in-hiv-1-controllers-and-htlv-2-co-infected-patients-with-a-history-of-injection-drug-use
#2
Ezequiel Ruiz-Mateos, María J Ruiz-León, Laura Tarancón-Díez, Carolina Gutiérrez, Fernando Dronda, Beatriz Domínguez-Molina, María J Pérez-Elías, Ana Moreno, Manuel Leal, Santiago Moreno, Alejandro Vallejo
HTLV-2/HIV-1-coinfected patients and HIV-infected patients with natural HIV-1 control show an immune capacity that allows some control of viral infections. These two groups of patients have showed an immune capacity that allows them to have some control over viral infections, very strong control of HIV-1 replication in the case of HIV-1 controllers. The purpose of this retrospective cross-sectional study was to compare viral and immunologic parameters between three cohorts of Caucasian adult HIV-1-infected patients, including HIV-1 controllers (29 patients), HTLV-2/HIV-1 chronic progressors (56 patients), and HIV-1 chronic progressors (101 patients), followed in two different tertiary University Hospitals in Spain...
February 15, 2019: Virus Research
https://read.qxmd.com/read/30769005/erap1-allotypes-impact-the-epitope-repertoire-of-virus-specific-cd8-t-cell-responses-in-acute-hepatitis-c-virus-infection
#3
Janine Kemming, Emma Reeves, Katja Nitschke, Vanessa Widmeier, Florian Emmerich, Tobias Hermle, Emma Gostick, Andreas Walker, Jörg Timm, David A Price, Maike Hofmann, Robert Thimme, Edward James, Christoph Neumann-Haefelin
BACKGROUND & AIMS: Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are linked with human leukocyte antigen (HLA) class I-associated autoinflammatory disorders, including ankylosing spondylitis and Behçet's disease. Disease-associated ERAP1 allotypes exhibit distinct functional properties, but it remains unclear how differential peptide trimming in vivo affects the repertoire of epitopes presented to CD8+ T cells. The aim of this study was to determine the impact of ERAP1 allotypes on the virus-specific CD8+ T cell epitope repertoire in an HLA-B*27:05+ individual with acute hepatitis C virus (HCV) infection...
February 12, 2019: Journal of Hepatology
https://read.qxmd.com/read/30764780/evidence-of-sustained-reductions-in-the-relative-risk-of-acute-hepatitis-b-and-c-virus-infections-and-the-increasing-burden-of-hepatitis-a-virus-infection-in-egypt-comparison-of-sentinel-acute-viral-hepatitis-surveillance-results-2001-17
#4
Maha Talaat, Salma Afifi, Erik J Reaves, Hanaa Abu Elsood, Amany El-Gohary, Samir Refaey, Radi Hammad, Mostafa Abdel Fadeel, Amr Kandeel
BACKGROUND: Egypt ranks fifth for the burden of viral hepatitis worldwide. As part of Egypt's renewed national strategy for the elimination of viral hepatitis, surveillance for acute viral hepatitis (AVH) was re-established during 2014-2017 to describe the current epidemiology and associated risk factors, and changes from surveillance conducted during 2001-2004. METHODS: Patients with suspected AVH were enrolled, completed a questionnaire, and provided blood for testing for hepatitis viruses A (HAV), B (HBV), C (HCV), D, and E (HEV) infections by enzyme-linked immunosorbent assay...
February 14, 2019: BMC Infectious Diseases
https://read.qxmd.com/read/30761547/frequency-and-implications-of-myeloid-derived-suppressor-cells-and-lymphocyte-subsets-in-egyptian-patients-with-hepatitis-c-virus-related-hepatocellular-carcinoma
#5
Helal F Hetta, Asmaa M Zahran, Shima G Mansor, Mohamed O Abdel-Malek, Mohamed A Mekky, Wael A Abbas
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in tumor immunity and induction of immune tolerance to a variety of antitumor effectors, including T-lymphocytes. Herein, we tried to evaluate the frequency and clinical significance of MDSCs and different lymphocyte subsets in HCV- related hepatocellular carcinoma (HCC). METHODS: Four groups were enrolled; chronic HCV (CHC, n=40), HCV related liver cirrhosis (HCV-LC, n= 40), HCV related HCC (HCV-HCC, n=75) and healthy control group (n=20)...
February 13, 2019: Journal of Medical Virology
https://read.qxmd.com/read/30747617/expression-of-human-ficolin-2-in-hepatocytes-confers-resistance-to-infection-by-diverse-hepatotropic-viruses
#6
Paywast J Jalal, Richard A Urbanowicz, Emma Horncastle, Monika Pathak, Chun Goddard, Amanj Saeed, Christopher P Mason, Jonathan K Ball, William L Irving, C Patrick McClure, Barnabas J King, Alexander W Tarr
The liver-expressed pattern recognition receptors mannose-binding lectin (MBL), ficolin-2 and ficolin-3 contribute to the innate immune response by activating complement. Binding of soluble ficolin-2 to viral pathogens can directly neutralize virus entry. We observed that the human hepatoma cell line HuH7.5, which is routinely used for the study of hepatotropic viruses, is deficient in expression of MBL, ficolin-2 and ficolin-3. We generated a cell line that expressed and secreted ficolin-2. This cell line (HuH7...
February 12, 2019: Journal of Medical Microbiology
https://read.qxmd.com/read/30735121/microrna-122-supports-robust-innate-immunity-in-hepatocytes-by-targeting-the-rtks-stat3-signaling-pathway
#7
Hui Xu, Shi-Jun Xu, Shu-Juan Xie, Yin Zhang, Jian-Hua Yang, Wei-Qi Zhang, Man-Ni Zheng, Hui Zhou, Liang-Hu Qu
MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and a central player in liver biology and disease. Herein, we report a previously unknown role for miR-122 in hepatocyte intrinsic innate immunity. Restoring miR-122 levels in hepatoma cells markedly enhanced the activation of interferons (IFNs) in response to a variety of viral nucleic acids or simulations, especially of hepatitis C virus RNA and poly (I:C). Mechanistically, miR-122 down-regulated the phosphorylation (Tyr705) of STAT3 and thereby removed the negative regulation of STAT3 on IFN-signaling...
February 8, 2019: ELife
https://read.qxmd.com/read/30713032/early-high-levels-of-regulatory-t-cells-and-t-helper-1-may-predict-the-progression-of-recurrent-hepatitis-c-after-liver-transplantation
#8
K Ghazal, O Morales, C Barjon, G Dahlqvist, L Aoudjehane, L Ouaguia, N Delhem, F Conti
BACKGROUND: Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS: Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed...
January 31, 2019: Clinics and Research in Hepatology and Gastroenterology
https://read.qxmd.com/read/30709707/hepatitis-c-virus
#9
Thomas Pietschmann, Richard J P Brown
Hepatitis C virus (HCV) is an enveloped, RNA virus transmitted through blood-to-blood contact. It infects humans only and primarily targets liver cells. HCV evades innate and adaptive immunity and establishes chronic infections in 70% of cases. If untreated, 20% of patients develop liver cirrhosis, and a fraction of these progress to hepatocellular carcinoma. Annually, 400000 patients die globally due to HCV infection. Direct-acting antivirals (DAAs) are licensed and target three viral proteins: the NS3-4A protease needed for processing the viral polyprotein, the NS5A phosphoprotein that regulates RNA replication and virus assembly, and the viral RNA-dependent RNA polymerase (NS5B) that catalyzes genome replication...
January 29, 2019: Trends in Microbiology
https://read.qxmd.com/read/30706858/expression-and-immune-recognition-of-polypeptides-derived-from-hepatitis-c-virus-structural-proteins
#10
Alyaa S Abdel Halim, Mohamed R Mohamed, Fatma F Abdel Hamid, Amr M Karim
Background: Hepatitis C virus (HCV) is characterized by a high degree of nucleotide sequence variability between genotypes. This variability extends to functional and immunological determinants. Serological tests using antigenic segments derived from the HCV polyprotein have been used for the diagnosis of HCV infection. However, available diagnostic Kits do not necessarily take type variability into consideration and are not optimized for HCV genotype 4a (HCV4a ), the predominant genotype in Egypt...
January 2019: Indian Journal of Pathology & Microbiology
https://read.qxmd.com/read/30700937/human-immunodeficiency-virus-and-hepatotropic-viruses-co-morbidities-as-the-inducers-of-liver-injury-progression
#11
REVIEW
Murali Ganesan, Larisa Y Poluektova, Kusum K Kharbanda, Natalia A Osna
Hepatotropic viruses induced hepatitis progresses much faster and causes more liver- related health problems in people co-infected with human immunodeficiency virus (HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus (HBV) and hepatitis C virus (HCV) causes significant numbers of non-acquired immune deficiency syndrome (AIDS)-related deaths in co-infected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported...
January 28, 2019: World Journal of Gastroenterology: WJG
https://read.qxmd.com/read/30687530/the-association-between-helicobacter-pylori-infection-and-liver-and-biliary-tract-disorders
#12
D Popescu, D Andronescu, P A Babes
Helicobacter Pylori (HP) persistently colonizes the stomach in about 50% of the globe population and it is the main risk factor for peptic ulcer, as well as for gastric adenocarcinoma and MALT gastric lymphoma. The treatment for HP revolutionized the management of the peptic ulcer disease, providing permanent healing in many cases. Preventing colonization of HP would be the primary prevention of gastric malignancy and peptic ulceration. At the same time, the presence of HP provides protection for some diseases (gastroesophageal reflux disease and its complications, esophageal adenocarcinoma, asthma), the eradication of the microorganism having negative repercussions...
April 2018: Current Health Sciences Journal
https://read.qxmd.com/read/30686790/cd56-negative-nk-cells-with-impaired-effector-function-expand-in-cmv-and-ebv-co-infected-healthy-donors-with-age
#13
Bojana Müller-Durovic, Jasmin Grählert, Oliver P Devine, Arne N Akbar, Christoph Hess
Natural killer cells lacking expression of CD56 (CD56neg NK cells) have been described in chronic HIV and hepatitis C virus infection. Features and functions of CD56neg NK cells in the context of latent infection with CMV and / or EBV with age are not known. In a cohort of healthy donors >60 years of age, we found that co-infection with CMV and EBV drives expansion of CD56neg NK cells. Functionally, CD56neg NK cells displayed reduced cytotoxic capacity and IFN-γ production, a feature that was enhanced with CMV / EBV co-infection...
January 27, 2019: Aging
https://read.qxmd.com/read/30686706/gaps-in-ambulatory-patient-safety-for-immunosuppressive-specialty-medications
#14
Sarah Patterson, Gabriela Schmajuk, Michael Evans, Ishita Aggarwal, Zara Izadi, Milena Gianfrancesco, Jinoos Yazdany
OBJECTIVES: New specialty drugs such as biologics are now available in record numbers, presenting increased safety risks for people with immune-mediated diseases. However, comprehensive assessments of patient safety for these drugs are lacking. We examined performance on key patient safety measures, such as screening for latent tuberculosis (LTBI), hepatitis B virus (HBV), and hepatitis C virus (HCV), for new users of a broad group of specialty medications. METHODS: Data were extracted via electronic health record data warehouses of a large university health system using structured queries, and extensive chart review was performed to confirm measure elements...
January 24, 2019: Joint Commission Journal on Quality and Patient Safety
https://read.qxmd.com/read/30684506/time-association-between-hepatitis-c-therapy-and-hepatocellular-carcinoma-emergence-in-cirrhosis-relevance-of-non-characterized-nodules
#15
Zoe Mariño, Anna Darnell, Sabela Lens, Victor Sapena, Alba Díaz, Ernest Belmonte, Christie Perelló, Jose Luis Calleja, Maria Varela, Manuel Rodriguez, Carlos Rodriguez de Lope, Susana Llerena, Xavier Torras, Adolfo Gallego, Margarita Sala, Rosa María Morillas, Beatriz Minguez, Jordi Llaneras, Susana Coll, José Antonio Carrion, Mercedes Iñarrairaegui, Bruno Sangro, Ramón Vilana, Manel Sole, Carmen Ayuso, José Ríos, Xavier Forns, Jordi Bruix, María Reig
BACKGROUND & AIMS: Despite the very high efficacy of direct acting antivirals (DAA) to eradicate hepatitis C virus infection, the impact on hepatocellular carcinoma development remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing hepatocellular carcinoma. METHODS: Retrospective, multicenter study focusing on cirrhotic patients treated with direct acting antivirals until December 2016...
January 23, 2019: Journal of Hepatology
https://read.qxmd.com/read/30680891/progressive-multifocal-leukoencephalopathy-secondary-to-hepatitis-c-virus-infection-related-t-cell-lymphopenia
#16
Ar Kar Aung, Jessica Robinson, Penelope Hey, Mahalia Lehmann, Yan Chow, Richard J Stark, Julian J Bosco
Progressive multifocal leukoencephalopathy (PML) is an uncommon neurological condition known to occur in the setting of T-cell immune suppression. We report a case of hepatitis C virus (HCV) infection-related T-cell lymphopenia manifesting as PML. HCV treatment and transient viral suppression resulted in immunological recovery with clinical stabilisation.
January 2019: Internal Medicine Journal
https://read.qxmd.com/read/30679972/potential-pathogenic-mechanisms-involved-in-the-association-between-lichen-planus-and-hepatitis-c-virus-infection
#17
REVIEW
Simona Roxana Georgescu, Mircea Tampa, Madalina Irina Mitran, Cristina Iulia Mitran, Maria Isabela Sarbu, Ilinca Nicolae, Clara Matei, Constantin Caruntu, Monica Neagu, Mircea Ioan Popa
Lichen planus (LP) is an immune-mediated inflammatory disease that particularly affects the skin and mucous membranes. Its etiology remains elusive, however some trigger factors, including viral or bacterial antigens, drugs and metals, have been postulated. There is a higher prevalence of hepatitis C virus (HCV) infection among patients with LP, with some geographical variations. HCV is an enveloped RNA virus that belongs to the Flaviviridae family and in most instances causes chronic liver infections. It has been hypothesized that HCV may contribute to LP development, but the link between the two disorders is not fully understood...
February 2019: Experimental and Therapeutic Medicine
https://read.qxmd.com/read/30678964/the-adjuvant-effect-of-c-60-oh-22-nanoparticles-promoting-both-humoral-and-cellular-immune-responses-to-hcv-recombinant-proteins
#18
Jing Liu, Xiaoyan Feng, Zhiyun Chen, Xiqin Yang, Ziyi Shen, Mengyu Guo, Fangling Deng, Ying Liu, Heqiu Zhang, Chunying Chen
Hepatitis c virus (HCV) infection is one of major causes for chronic liver diseases worldwide and could lead to death. Development of effective HCV vaccines is a powerful auxiliary method of existing treatments. Adjuvants are necessary for modern vaccines to promote immune responses. Among the various nanomaterials that have been developed, multihydroxylated fullerene (C60 (OH)22 ) has been proved as an efficient adjuvant for human immunodeficiency virus DNA vaccine. Here, we utilized three types of HCV recombinant proteins as antigens to investigate the activity of C60 (OH)22 as a protein vaccine adjuvant...
April 2019: Materials Science & Engineering. C, Materials for Biological Applications
https://read.qxmd.com/read/30674625/potent-anti-hepatitis-c-hcv-t-cell-immune-responses-induced-in-mice-vaccinated-with-dna-launched-rna-replicons-and-mva-hcv
#19
María Q Marín, Patricia Pérez, Karl Ljungberg, Carlos Óscar S Sorzano, Carmen E Gómez, Peter Liljeström, Mariano Esteban, Juan García-Arriaza
Hepatitis C is a liver disease caused by the Hepatitis C virus (HCV) affecting 71 million people worldwide with no licensed vaccines that prevent infection. Here, we have generated four novel alphavirus-based DNA-launched self-amplifying RNA replicon (DREP) vaccines expressing either structural Core-E1-E2 or nonstructural p7-NS2-NS3 HCV proteins of genotype 1a placed under the control of an alphavirus promoter, with or without an alphaviral translational enhancer (grouped as DREP-HCV and DREP-e-HCV, respectively)...
January 23, 2019: Journal of Virology
https://read.qxmd.com/read/30670689/the-circadian-clock-components-bmal1-and-rev-erb%C3%AE-regulate-flavivirus-replication
#20
Xiaodong Zhuang, Andrea Magri, Michelle Hill, Alvina G Lai, Abhinav Kumar, Srinivasa Bhargav Rambhatla, Claire L Donald, Andrea F Lopez-Clavijo, Simon Rudge, Katherine Pinnick, Wai Hoong Chang, Peter A C Wing, Ryan Brown, Ximing Qin, Peter Simmonds, Thomas F Baumert, David Ray, Andrew Loudon, Peter Balfe, Michael Wakelam, Sam Butterworth, Alain Kohl, Catherine L Jopling, Nicole Zitzmann, Jane A McKeating
The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome replication. Genetic knock out of Bmal1 and over-expression or activation of REV-ERB with synthetic agonists inhibits the replication of HCV and the related flaviruses dengue and Zika via perturbation of lipid signaling pathways...
January 22, 2019: Nature Communications
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