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Ahmad Ayadi, Amir Hossein Nafari, Shiva Irani, Elham Mohebbi, Fahimeh Mohebbi, Fatemeh Sakhaee, Farzam Vaziri, Seyed Davar Siadat, Abolfazl Fateh
Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta-thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity...
February 18, 2019: Journal of Cellular Biochemistry
Emi Inoue-Shinomiya, Miyako Murakawa, Yasuhiro Asahina, Mina Nakagawa, Jun Tsuchiya, Ayako Sato, Tomoyuki Tsunoda, Masato Miyoshi, Sayuri Nitta, Fukiko Kawai-Kitahata, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Kazumoto Murata, Masashi Mizokami, Mamoru Watanabe
AIM: Although the efficacy of hepatitis C virus (HCV) treatment is improved dramatically by direct-acting antiviral agents (DAAs), the assessment of hepatocellular carcinoma (HCC) remains important. Interferon lambda 3 (IFN-λ3) is associated with liver fibrosis and inflammation in chronic hepatitis C (CHC) patients, but its impact on carcinogenesis remains controversial and little is known about its effects after viral clearance. To determine the contribution of IFN-λ3 to hepatocarcinogenesis after HCV clearance, we analyzed IFNL3 genotypes and serial serum IFN-λ3 levels in CHC patients who achieved sustained virological responses (SVR)...
January 9, 2019: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Ikram Sghaier, Etienne Brochot, Besma Y Loueslati, Wassim Y Almawi
HCV has been associated with pro-inflammatory state, which predisposes to liver cancer such as hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on the HCC progression have remained unclear. Although HCV infection illustrates the role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment-induced HCV eradication. In the present study, we studied the possible role of HCV infection in the processes of HCC initiation, and we performed a systemic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein-proteins interactions (PPI) networks...
January 6, 2019: Reviews in Medical Virology
Katerina Kassela, Ioannis Karakasiliotis, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Stavroula Veletza, Maria Panopoulou, John Koskinas, Konstantinos Mimidis, Penelope Mavromara
Background: Intergenotypic recombinant hepatitis C virus (HCV) strains emerge rarely during coinfection of the same individual with two HCV genotypes. Few recombinant HCV strains have been identified to date and only one, CRF01 2k/1b, has become a worldwide concern. This study reevaluated the genotyping of three HCV genotype 2 strains from a group of patients with an unusually low rate of sustained virological response after pegylated interferon/ribavirin treatment. In addition, genetic determinants of host interferon resistance were evaluated...
January 2019: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
Candelaria Vergara, Chloe L Thio, Eric Johnson, Alex H Kral, Thomas R O'Brien, James J Goedert, Alessandra Mangia, Valeria Piazzolla, Shruti H Mehta, Gregory D Kirk, Arthur Y Kim, Georg M Lauer, Raymond T Chung, Andrea L Cox, Marion G Peters, Salim I Khakoo, Laurent Alric, Matthew E Cramp, Sharyne M Donfield, Brian R Edlin, Michael P Busch, Graeme Alexander, Hugo R Rosen, Edward L Murphy, Rachel Latanich, Genevieve L Wojcik, Margaret A Taub, Ana Valencia, David L Thomas, Priya Duggal
BACKGROUND & AIMS: Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry...
December 26, 2018: Gastroenterology
Fernanda Rodrigues-Soares, Guilherme Suarez-Kurtz
We searched Pubmed entries and the Lattes database for Brazilian Pharmacogenetics Network investigators, for pharmacogenetic/genomic (PGx) studies in the Brazilian population, focusing on the drugs and genes included in the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Warfarin was the most extensively studied drug in a PGx context: a Genome-Wide Association Study targeting warfarin stable dose identified significant signals in VKORC1 and CYP2C9, several PGx dosing algorithms were developed based on these and other genes, and the implications of population admixture on extrapolation of dosing recommendations in the CPIC guidelines were examined...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
Chaturaka Rodrigo, Preston Leung, Andrew R Lloyd, Rowena A Bull, Fabio Luciani, Jason Grebely, Gregory J Dore, Tanya Applegate, Kimberly Page, Julie Bruneau, Andrea L Cox, William Osburn, Arthur Y Kim, Naglaa H Shoukry, Georg M Lauer, Lisa Maher, Janke Schinkel, Maria Prins, Margaret Hellard, Auda A Eltahla
Interactions between the host immune system and the viral variants determine persistence of hepatitis C virus (HCV) infection after the acute phase of infection. This study describes the genetic variability of within-host HCV viral variants in acute infection and correlates it with host and virus-related traits and infection outcome. Next generation sequence data (Illumina, MiSeq platform) of viral genomes from 116 incident acute infections (within 180 days of infection) were analysed to determine all the single nucleotide polymorphism (SNP) frequencies above a threshold of 0...
December 22, 2018: Journal of Viral Hepatitis
Lisa Schmidtke, Katharina Schrick, Sabrina Saurin, Rudolf Käfer, Fabian Gather, Julia Weinmann-Menke, Hartmut Kleinert, Andrea Pautz
Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell function. Therefore, it is important to identify cellular mechanisms involved in the control of type III IFN expression. All IFN family members contain AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) of their mRNAs that determine mRNA half-life and consequently the expressional level of these cytokines...
December 21, 2018: Biochemical Journal
Isabella Esposito, Sebastián Marciano, Leila Haddad, Omar Galdame, Alejandra Franco, Adrián Gadano, Diego Flichman, Julieta Trinks
This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a...
December 21, 2018: Viruses
Anwar Jamal Khan, Vivek Aanand Saraswat, Prabhat Ranjan, Devendra Parmar, Tajwar Singh Negi, Samir Mohindra
Hepatitis C virus infection is a considerable public-health problem and an important cause of liver disease with about 71 million people infected worldwide and more than 399,000 people die every year from hepatitis C related liver diseases. The present study was therefore, initiated to investigate the association of polymorphism in interferon lamda-3 (IFNL3) also known as Interleukin-28B (IL28B) gene with chronic HCV infection and association of these polymorphic variants with the combination daclatasvir and sofosbuvir HCV therapy response...
November 15, 2018: Journal of Medical Virology
Stéphanie Bibert, Agnieszka Wójtowicz, Patrick Taffé, Philip E Tarr, Enos Bernasconi, Hansjakob Furrer, Huldrych F Günthard, Matthias Hoffmann, Laurent Kaiser, Michael Osthoff, Jacques Fellay, Matthias Cavassini, Pierre-Yves Bochud
BACKGROUND: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections. OBJECTIVES: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS)...
November 28, 2018: AIDS
Ji-Yih Chen, Chin-Man Wang, Tai-Di Chen, Yeong-Jian Jan Wu, Jing-Chi Lin, Ling Ying Lu, Jianming Wu
BACKGROUND: Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. METHODS: TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan...
August 29, 2018: Arthritis Research & Therapy
Lai Wei, Heiner Wedemeyer, Yun-Fan Liaw, Henry Lik-Yuen Chan, Teerha Piratvisuth, Patrick Marcellin, Jidong Jia, Deming Tan, Wan-Cheng Chow, Maurizia R Brunetto, Moisés Diago, Selim Gurel, Viacheslav Morozov, Hua He, Yonghong Zhu, Cynthia Wat, Bernadette Surujbally, Alexander J Thompson
BACKGROUND & AIMS: It has yet to be firmly established whether host IFNL3 (IL28B) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the IFNL3 region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies. METHODS: Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment)...
2018: PloS One
Martin Palus, Yahya Sohrabi, Karl W Broman, Hynek Strnad, Matyáš Šíma, Daniel Růžek, Valeriya Volkova, Martina Slapničková, Jarmila Vojtíšková, Lucie Mrázková, Jiří Salát, Marie Lipoldová
BACKGROUND: Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, carrying 12...
July 6, 2018: BMC Neuroscience
Thuy Thu Nguyen, Shoichi Suzuki, Ryuichi Sugamata, Fuyu Ito, Dat Huu Tran, Tomoko Yamamoto, Shoji Kawachi, Kazuo Suzuki
Pattern recognition receptors recognize RNA viruses and trigger type I and III interferon (IFN) production and apoptosis to limit viral replication and spread. Some innate immune cells produce oxidants in response to viral infection to protect against invasion. Recent studies have demonstrated the virucidal activity of hypothiocyanous acid (HOSCN), an oxidant generated by the peroxidase-catalyzed reaction of thiocyanate with hydrogen peroxide. However, the effects of HOSCN on host antiviral responses are still unknown...
June 2018: Tohoku Journal of Experimental Medicine
Zhe Xie, Yuantao Li, Lu Long, Hua Liang, Weiping Cai, Tao Shen
BACKGROUND: Female gender and favorable IFNL3 genotypes are the primary independent predictors of spontaneous clearance of HCV infection. However, chronic hepatitis C infection occurs in numerous women carrying favorable IFNL3 genotypes, indicating that other host and/or virological factors contribute to the prognosis of infection. METHODS: A cohort of 137 anti-HCV-positive female Han Chinese cases, including 64 chronic HCV carriers and 73 HCV spontaneous resolvers, was recruited in the study...
June 4, 2018: BMC Infectious Diseases
Pratichi Singh, J Febin Prabhu Dass
IFNL3 gene plays a crucial role in immune defense against viruses. It induces the interferon stimulated genes (ISGs) with antiviral properties by activating the JAK-STAT pathway. In this study, we investigated the evolutionary force involved in shaping the IFNL3 gene to perform its downstream function as a regulatory gene in HCV clearance. We have selected 25 IFNL3 coding sequences with human gene as a reference sequence and constructed a phylogeny. Furthermore, rate of variation, substitution saturation test, phylogenetic informativeness and differential selection were also analysed...
May 7, 2018: Progress in Biophysics and Molecular Biology
Kunyan Qiao, Congdoanh Trieu, Zhixiao Huo, Yanan Du, Wei Hou
BACKGROUND: Two single-nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G), near the interleukin 28B (IL28B, also known as IFN lambda-3, IFNL3) gene, have a strong association with both spontaneous and treatment-induced hepatitis C virus (HCV) clearance. IL28B polymorphisms have shown a marked differential distribution with regional and ethnic variation. The study aimed to investigate the distribution of IL28B rs12979860 and rs8099917 genotypes in patients with chronic hepatitis C (CHC) in Tianjin, China...
April 1, 2018: Clinical Laboratory
Adrian Egli, Jyotshna Mandal, Desiree M Schumann, Michael Roth, Brad Thomas, D Lorne Tyrrell, Francesco Blasi, Kostantinos Kostikas, Wim Boersma, Branislava Milenkovic, Alicia Lacoma, Katharina Rentsch, Gernot G U Rohde, Renaud Louis, Joachim G Aerts, Tobias Welte, Antoni Torres, Michael Tamm, Daiana Stolz
BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months...
March 21, 2018: BMC Pulmonary Medicine
A J Walker, C J Peacock, V Pedergnana, W L Irving
Hepatitis C virus (HCV)-infected patients are at risk of developing hepatocellular carcinoma (HCC). Individuals at heightened risk could be targeted by intensive follow-up surveillance. We have conducted a systematic review of the literature to identify host genetic predisposition to HCC in HCV-infected patients. A comprehensive search of Medline and Embase databases was performed, and the strength of evidence of associations for each gene on development of HCC was evaluated. We identified 166 relevant studies, relating to 137 different genes, or combinations thereof...
May 2018: Journal of Viral Hepatitis
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