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Interferons and viral infections

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https://www.readbyqxmd.com/read/28109003/eradication-of-hcv-and-non-liver-related-non-aids-related-events-in-hiv-hcv-coinfection
#1
Juan Berenguer, Elena Rodríguez-Castellano, Ana Carrero, Miguel A Von Wichmann, Marta Montero, María J Galindo, Josep Mallolas, Manuel Crespo, María J Téllez, Carmen Quereda, José Sanz, Carlos Barros, Cristina Tural, Ignacio Santos, Federico Pulido, Josep M Guardiola, Rafael Rubio, Enrique Ortega, María L Montes, Juan J Jusdado, Gabriel Gaspar, Herminia Esteban, José M Bellón, Juan González-García
: We assessed non-liver-related non-AIDS-related (NLR-NAR) events and mortality in a cohort of HIV/HCV-coinfected patients treated with interferon and ribavirin between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and non-responders. Fine and Gray regression analysis was conducted to determine the adjusted sub-hazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk...
January 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#2
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28107471/high-serum-lipopolysaccharide-binding-protein-level-in-chronic-hepatitis-c-viral-infection-is-reduced-by-anti-viral-treatments
#3
Hsiao-Ching Nien, Shih-Jer Hsu, Tung-Hung Su, Po-Jen Yang, Jin-Chuan Sheu, Jin-Town Wang, Lu-Ping Chow, Chi-Ling Chen, Jia-Horng Kao, Wei-Shiung Yang
BACKGROUND: Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon...
2017: PloS One
https://www.readbyqxmd.com/read/28107341/complex-dynamics-of-virus-spread-from-low-infection-multiplicities-implications-for-the-spread-of-oncolytic-viruses
#4
Ignacio A Rodriguez-Brenes, Andrew Hofacre, Hung Fan, Dominik Wodarz
While virus growth dynamics have been well-characterized in several infections, data are typically collected once the virus population becomes easily detectable. Earlier dynamics, however, remain less understood. We recently reported unusual early dynamics in an experimental system using adenovirus infection of human embryonic kidney (293) cells. Under identical experimental conditions, inoculation at low infection multiplicities resulted in either robust spread, or in limited spread that eventually stalled, with both outcomes occurring with approximately equal frequencies...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28106111/broad-range-antiviral-activity-of-hydrogen-sulfide-against-highly-pathogenic-rna-viruses
#5
Nikolay Bazhanov, Olivier Escaffre, Alexander N Freiberg, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide is an important endogenous mediator that has been the focus of intense investigation in the past few years, leading to the discovery of its role in vasoactive, cytoprotective and anti-inflammatory responses. Recently, we made a critical observation that H2S also has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study we tested the antiviral and anti-inflammatory activity of the H2S slow-releasing donor GYY4137 on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104465/heroin-use-is-associated-with-lower-levels-of-restriction-factors-and-type-i-interferon-expression-and-facilitates-hiv-1-replication
#6
Jia-Wu Zhu, Feng-Liang Liu, Dan Mu, De-Yao Deng, Yong-Tang Zheng
Heroin use is associated with increased incidence of infectious diseases such as HIV-1 infection, as a result of immunosuppression to a certain extent. Host restriction factors are recently identified cellular proteins with potent antiviral activities. Whether heroin use impacts on the in vivo expression of restriction factors that result in facilitating HIV-1 replication is poorly understood. Here we recruited 432 intravenous drug users (IDUs) and 164 non-IDUs at high-risk behaviors. Based on serological tests, significantly higher prevalence of HIV-1 infection was observed among IDUs compared with non-IDUs...
January 16, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28102839/foot-and-mouth-disease-virus-infection-suppresses-autophagy-and-nf-%C3%B0%C2%BAb-antiviral-responses-via-degradation-of-atg5-atg12-by-3c-pro
#7
Xuxu Fan, Shichong Han, Dan Yan, Yuan Gao, Yanquan Wei, Xiangtao Liu, Ying Liao, Huichen Guo, Shiqi Sun
Autophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2-5 h...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102325/viral-micrornas-target-a-gene-network-inhibit-stat-activation-and-suppress-interferon-responses
#8
Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#9
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
: Interferon inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates including transmitted founder viruses is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100612/sex-dependent-intestinal-replication-of-an-enteric-virus
#10
Christopher M Robinson, Yao Wang, Julie K Pfeiffer
: Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100608/herpes-simplex-virus-type-1-ul24-abrogates-dna-sensing-signal-pathway-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#11
Haiyan Xu, Chenhe Su, Angela Pearson, Christopher H Mody, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of anti-viral genes such as type I interferons and production of inflammatory cytokines. HSV-1 UL24 is widely conserved among the herpesviruses family and is essential for efficient viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100256/transcriptomic-signatures-differentiate-survival-from-fatal-outcomes-in-humans-infected-with-ebola-virus
#12
Xuan Liu, Emily Speranza, César Muñoz-Fontela, Sam Haldenby, Natasha Y Rickett, Isabel Garcia-Dorival, Yongxiang Fang, Yper Hall, Elsa-Gayle Zekeng, Anja Lüdtke, Dong Xia, Romy Kerber, Ralf Krumkamp, Sophie Duraffour, Daouda Sissoko, John Kenny, Nichola Rockliffe, E Diane Williamson, Thomas R Laws, Magassouba N'Faly, David A Matthews, Stephan Günther, Andrew R Cossins, Armand Sprecher, John H Connor, Miles W Carroll, Julian A Hiscox
BACKGROUND: In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality. RESULTS: The data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection...
January 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28097103/efficacy-and-safety-of-daclatasvir-in-hepatitis-c-an-overview
#13
REVIEW
Nesrine Gamal, Stefano Gitto, Pietro Andreone
Hepatitis C virus (HCV) infection is a growing public health concern, with 184 million people infected worldwide. During the past decade, interferon has been the backbone of HCV treatment, even though it remains far from ideal. The latest development of the new direct antivirals has drastically changed the treatment approach for chronic hepatitis C (CHC). Inhibitors of the HCV NS5A region have garnered remarkable interest among treating physicians, due to their high potency and favourable safety profile. In particular, treatment with daclatasvir (DCV) has yielded high rates of vriologic response in patients infected with genotype (Gt) 1 and Gt 3, when used in combination with other antivirals of a different class, such as sofosbuvir...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28097101/novel-treatment-of-hepatitis-c-virus-infection-for-patients-with-renal-impairment
#14
REVIEW
Goki Suda, Koji Ogawa, Megumi Kimura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction, including patients undergoing hemodialysis (HD). The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease; fortunately, successful HCV eradication sometimes restore HCV-related renal dysfunction. Moreover, the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28095508/the-smc5-6-complex-restricts-hbv-when-localized-to-nd10-without-inducing-an-innate-immune-response-and-is-counteracted-by-the-hbv-x-protein-shortly-after-infection
#15
Congrong Niu, Christine M Livingston, Li Li, Rudolf K Beran, Stephane Daffis, Dhivya Ramakrishnan, Dara Burdette, Leanne Peiser, Eduardo Salas, Hilario Ramos, Mei Yu, Guofeng Cheng, Michel Strubin, William E Delaney Iv, Simon P Fletcher
The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions...
2017: PloS One
https://www.readbyqxmd.com/read/28092214/treatment-of-delta-hepatitis-today-and-in-the-future-a-review
#16
Ibrahim Halil Bahcecioglu, Abdurrahman Sahin
Hepatitis delta virus (HDV) is a defective satellite virus and propagates in the presence of Hepatitis B virus (HBV) surface antigen (HBsAg). Approximately 5% of the people who infected with HBV are also infected with HDV. Chronic hepatitis caused by delta is the most severe form of chronic viral hepatitis including accelerated fibrosis, liver decompensation and development of hepatocellular carcinoma. Interferon-based therapies still remain the only treatment option of the hepatitis delta. The beneficiary effects of the interferon-based therapies, however, stop frequently with termination of the given therapy and relapse rate is very high...
January 16, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28092171/a-pangenotypic-single-tablet-regimen-of-sofosbuvir-velpatasvir-for-the-treatment-of-chronic-hepatitis-c-infection
#17
Ilan S Weisberg, Ira M Jacobson
Hepatitis C virus (HCV) infects nearly 170 million people worldwide and is a leading cause of progressive liver damage, cirrhosis, and hepatocellular carcinoma. Curative therapies have historically relied on interferon-based treatments and were limited by significant toxicity and poor response rates, particularly among patients with prior treatment failure and advanced hepatic fibrosis. The recent advent of direct acting antiviral (DAA) agents which target key steps in the HCV viral life cycle has transformed the landscape of HCV treatment by offering highly effective and well tolerated interferon-free treatments...
January 16, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28089609/de-immunized-and-functional-therapeutic-deft-versions-of-a-long-lasting-recombinant-alpha-interferon-for-antiviral-therapy
#18
Eduardo F Mufarrege, Sofía Giorgetti, Marina Etcheverrigaray, Frances Terry, William Martin, Anne S De Groot
Interferon α (IFN-α) exerts potent antiviral, immunomodulatory, and antiproliferative activity and have proven clinical utility in chronic hepatitis B and C virus infections. However, repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described. So as to improve the in vivo biological efficacy of IFN-α, a long lasting hyperglycosylated protein (4N-IFN) derived from IFN-α2b wild type (WT-IFN) was developed...
January 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#19
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087685/bst-2-restricts-iav-release-and-is-countered-by-the-viral-m2-protein
#20
Siqi Hu, Lijuan Yin, Shan Mei, Jian Li, Fengwen Xu, Hong Sun, Xiaoman Liu, Shan Cen, Chen Liang, Ailing Li, Fei Guo
BST-2 (tetherin, CD317, HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In this study, we report that BST-2 diminishes the production of IAV virus-like particles, that are generated by viral NA and HA proteins, to a much greater degree than inhibits the production of wild type IAV particles. This relatively weaker inhibition of IAV is associated with reduction of BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to downregulation of cell surface BST-2 via the proteasomal pathway...
January 13, 2017: Biochemical Journal
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