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Interferons and viral infections

Tian-Sheng He, Tian Chen, Dan-Dan Wang, Liang-Guo Xu
Mitochondrial anti‑viral signaling protein (VISA), additionally termed MAVS, IPS‑1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig‑like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR‑VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKKε, as well as activation of NF‑κB, to induce type I interferons (IFNs) and pro‑inflammatory cytokines...
June 15, 2018: Molecular Medicine Reports
Jing Wang, Yujia Wang, Rui Zhou, Jianyuan Zhao, Yongxin Zhang, Dongrong Yi, Quanjie Li, Jinming Zhou, Fei Guo, Chen Liang, Xiaoyu Li, Shan Cen
The productive infection of influenza A virus (IAV) depends on host factors. However, the involvement of long non-coding RNAs (lncRNAs) in IAV infection remains largely uninvestigated. In this work, we have discovered a human lncRNA, named lncRNA-PAAN (PA-associated noncoding RNA) that enhances IAV replication. The level of lncRNA-PAAN increases upon infection of IAV, but not other viruses, nor interferon treatment, suggesting specific up-regulation of lncRNA-PAAN expression by IAV. Silencing lncRNA-PAAN significantly decreases IAV replication through impairing the activity of viral RNA-dependent RNA polymerase (RdRp)...
June 16, 2018: Viruses
Abid Shoukat, Mosin S Khan, Syed Mudassar, Zaffar Kawoosa, Altaf H Shah, Showkat Ali Zargar
Background: In hepatitis C virus (HCV), infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R) therapy and progression to chronic hepatitis C (CHC). Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24-48 weeks including 250 HCV infected patients...
April 2018: Journal of Global Infectious Diseases
Ismail Sebina, Ashraful Haque
Type I interferons are a family of cytokines with a wide range of biological activities including anti-viral and immune-regulatory functions. Here, we focus on the protozoan parasitic disease, malaria, and examine the effects of type I IFN-signalling during Plasmodium infection of humans and experimental mice. Since the 1960's, there have been many studies in this area, but a simple explanation for the role of type I IFN has not emerged. Although epidemiological data are consistent with roles for type I IFN in influencing malaria disease severity, functional proof of this remains sparse in humans...
June 16, 2018: Immunology
Ja-Young Kwon, Paulomi Aldo, Yuan You, Jiahui Ding, Karen Racicot, Xiaoyan Dong, John Murphy, Guy Glukshtad, Michelle Silasi, Jian Peng, Li Wen, Vikki M Abrahams, Roberto Romero, Gil Mor
Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens. Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications. Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties...
June 15, 2018: Cellular & Molecular Immunology
Bei Wang, Tze Hau Lam, Mun Kuen Soh, Zhiyong Ye, Jinmiao Chen, Ee Chee Ren
Human influenza virus (IAV) are among the most common pathogens to cause human respiratory infections. A better understanding on interplay between IAV and host factors may provide clues for disease prevention and control. While many viruses are known to downregulate p53 upon entering the cell to reduce the innate host antiviral response, IAV infection is unusual in that it activates p53. However, it has not been clear whether this process has proviral or antiviral effects. In this study, using human isogenic p53 wild-type and p53null A549 cells generated from the CRISPR/Cas9 technology, we observed that p53null cells exhibit significantly reduced viral propagation when infected with influenza A virus (strain A/Puerto Rico/8/1934 H1N1)...
2018: Frontiers in Immunology
Gregory C Valentine, Maxim D Seferovic, Stephanie W Fowler, Angela M Major, Rodion Gorchakov, Rebecca Berry, Alton G Swennes, Kristy O Murray, Melissa A Suter, Kjersti M Aagaard
BACKGROUND: Vertical transmission of Zika virus (ZIKV) leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital ZIKV infection may only become clinically apparent in the postnatal period. OBJECTIVES: We sought to develop an outbred mouse model of ZIKV vertical transmission to determine if the timing of gestational ZIKV exposure yields phenotypic differences at birth and through adolescence...
June 11, 2018: American Journal of Obstetrics and Gynecology
L Cedillo-Barrón, J García-Cordero, G Shrivastava, S Carrillo-Halfon, M León-Juárez, J Bustos Arriaga, Pc León Valenzuela, B Gutiérrez Castañeda
Flaviviruses are positive, single-stranded, enveloped cytoplasmic sense RNA viruses that cause a variety of important diseases worldwide. Among them, Zika virus, West Nile virus, Japanese encephalitis virus, and Dengue virus have the potential to cause severe disease. Extensive studies have been performed to elucidate the structure and replication strategies of flaviviruses, and current studies are aiming to unravel the complex molecular interactions between the virus and host during the very early stages of infection...
2018: Sub-cellular Biochemistry
Qinya Xie, Shengwen Chen, Renyun Tian, Xiang Huang, Rilin Deng, Binbin Xue, Yuwen Qin, Yan Xu, Jingjing Wang, Mengmeng Guo, Jinwen Chen, Songqing Tang, Guangdi Li, Haizhen Zhu
Emerging evidence indicates that long non-coding RNAs (lncRNAs) regulate various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and interferon (IFN) pathway remains largely unknown. Here, we report that lncRNA ITPRIP-1 (lncITPRIP-1) is involved in viral infection and plays a crucial role in virus-triggered IFN signaling pathway through targeting MDA5. LncITPRIP-1 can be induced by viral infection, which is not entirely dependent on IFN signal. Besides, there is no coding potential found in lncITPRIP-1 transcript...
June 13, 2018: Journal of Virology
Saskia D van Asten, Matthijs Raaben, Benjamin Nota, Robbert M Spaapen
Cellular antiviral programs can efficiently inhibit viral infection. These programs are often initiated through signaling cascades induced by secreted proteins such as type I interferons, IL-6 or TNF-α. Here, we generated an arrayed library of 756 human secreted proteins to perform a secretome screen focused on the discovery of novel modulators of viral entry and/or replication. The individual secreted proteins were tested for their capacity to inhibit infection by two replication-competent recombinant vesicular stomatitis viruses (VSV) with distinct glycoproteins utilizing different entry pathways...
June 13, 2018: Journal of Virology
Arif A Khan, Ruchi Srivastava, Hawa Vahed, Soumyabrata Roy, Sager S Walia, Grace J Kim, Mona A Fouladi, Taikun Yamada, Vincent T Ly, Cynthia Lam, Anthony Lou, Vivianna Nguyen, Undariya Boldbaatar, Roger Geertsema, Nigel W Fraser, Lbachir BenMohamed
Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in Human Leukocyte Antigen- (HLA-) transgenic rabbit model of ocular herpes (HLA Tg rabbit). Three asymptomatic (ASYMP) peptide epitopes were selected from the HSV-1 membrane glycoprotein C (UL44400-408 ), the DNA replication binding helicase (UL9196-204 ), and the tegument protein (UL25572-580 ), all preferentially recognized by CD8+ T cells from "naturally protected" HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease)...
June 13, 2018: Journal of Virology
Wenjia Chai, Jing Li, Qilin Shangguan, Qi Liu, Xinda Li, Dandan Qi, Xiaomei Tong, Wenjun Liu, Xin Ye
LncRNAs are involved in many aspects of cellular processes, including antiviral immune response. To identify influenza A virus (IAV)-related lncRNAs, we performed RNA-deep sequencing to compare the profiles of lncRNAs in A549 and 293T cells with or without IAV infection. We identified an IAV-upregulated lncRNA named lnc-ISG20 because it shares most of its sequence with ISG20. We found that lnc-ISG20 is an interferon-stimulated gene similar to ISG20. Overexpression of lnc-ISG20 inhibited IAV replication, while lnc-ISG20 knockdown favored viral replication, suggesting that ln-ISG20 is inhibitory to IAV replication...
June 13, 2018: Journal of Virology
Jeroen Witteveldt, Alasdair Ivens, Sara Macias
Type I interferons (IFNs) are central components of the antiviral response. Most cell types respond to viral infections by secreting IFNs, but the mechanisms that regulate correct expression of these cytokines are not completely understood. Here, we show that activation of the type I IFN response regulates the expression of miRNAs in a post-transcriptional manner. Activation of IFN expression alters the binding of the Microprocessor complex to pri-miRNAs, reducing its processing rate and thus leading to decreased levels of a subset of mature miRNAs in an IRF3-dependent manner...
June 12, 2018: Cell Reports
Nidhi Kaushik, Saumya Anang, Krishna Priya Ganti, Milan Surjit
Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Owing to its feco oral transmission route, sporadic as well as epidemic outbreaks recurrently occur. No specific antiviral therapy is available against the disease caused by HEV. Broad spectrum antivirals such as ribavirin and interferon alfa are prescribed in severe and chronic HEV cases. However, the side effects, cost, and limitations of usage render the available treatment unsuitable for several categories of patients. We recently reported the ability of zinc to inhibit viral replication in mammalian cell culture models of HEV infection...
June 13, 2018: DNA and Cell Biology
John T Crowl, Daniel B Stetson
Detection of nucleic acids by innate immune sensors triggers the production of type I interferons (IFNs). While IFNs are essential for host defense against viral infection, dysregulated production of IFNs underlies numerous autoinflammatory diseases. We have found that the loss of sumoylation results in a potent, spontaneous IFN response. Vertebrates possess three small ubiquitin-like modifiers (SUMOs) that can be conjugated onto target proteins and alter protein function in diverse but still poorly characterized ways...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yu-Li Lin, Pei-Yun Cheng, Chiao-Li Chin, Li-Min Huang, Shr-Yu Lin, Bor-Luen Chiang
To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine...
June 8, 2018: Vaccine
Abdul-Quddus Mohammed, Ranshaka Auckle, Hai-Ling Li, Si-Ling Xu, Lu Liu, Dong-Dong Zhao, Wen-Liang Che
BACKGROUND: Pegylated interferon (pegIFN) in combination with ribavirin (RBV) has successfully improved the rate of sustained virological response (SVR) in chronic hepatitis C virus (HCV) infected individuals, which reduces the progression of the chronic liver disease. However, the influence of combination therapy (pegIFN/RBV) on cardiac function has yielded ambiguous results. The present study aimed to evaluate the effects of combination therapy with pegIFN/RBV on cardiac function of HCV-infected individuals with SVR...
June 2018: American Journal of the Medical Sciences
Camilly P Pires de Mello, George L Drusano, Jaime L Rodriquez, Ajeet Kaushik, Ashley N Brown
Dengue virus (DENV) is the most prevalent mosquito-borne viral illness in humans. Currently, there are no therapeutic agents available to prevent or treat DENV infections. Our objective was to fill this unmet medical need by evaluating the antiviral activity of interferon-α (IFN) and ribavirin (RBV) as a combination therapy against DENV. DENV-infected Vero and Huh-7 cells were exposed to RBV and/or IFN, and the viral burden was quantified over time by plaque assay. Drug-drug interactions for antiviral effect were determined by fitting a mathematical model to the data...
June 9, 2018: Viruses
Kenza A Mansoor, Fadi Qadan, Mathias Schmidt, Nidal A Qinna, Mujtaba Badr, Khalid Z Matalka
Background : Viral influenza infection causes serious health issues especially when an outbreak occurs. Although influenza virus vaccines are available and each year manufactures modify the vaccine depending on the expected mutated strain, it is still far from satisfactory, mainly in young children and older adults. Therefore, a product that can support and shape the immune system to protect against viral flu infections is highly essential. Methods : A functional food water-soluble mixture of pomegranate, red grape, dates, olive fruit, figs, and ginger extracts, termed herein “Protector”, was prepared and tested in stimulating/modulating the production of specific cytokines, and hemagglutinin inhibition (HAI) antibodies following viral flu vaccination in mice...
June 8, 2018: Nutrients
Giada Frascaroli, Carina Lecher, Stefania Varani, Corinna Setz, Johannes van der Merwe, Wolfram Brune, Thomas Mertens
Human cytomegalovirus (HCMV) persistently infects 40-90% of the human population but in the face of a normal immune system, viral spread and dissemination are efficiently controlled thus preventing clinically signs and disease. HCMV-infected hosts produce a remarkably large amount of HCMV-specific CD4+ and CD8+ T cells that can even reach 20-50% of total T memory cells in the elderly. How HCMV may elicit such large and long-lasting T-cell responses in the absence of detectable viremia has not been elucidated yet...
2018: Frontiers in Immunology
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