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Interferons and viral infections

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https://www.readbyqxmd.com/read/29053745/impact-of-the-structural-integrity-of-the-three-way-junction-of-adenovirus-vai-rna-on-pkr-inhibition
#1
Edis Dzananovic, Astha, Grzegorz Chojnowski, Soumya Deo, Evan P Booy, Pauline Padilla-Meier, Kevin McEleney, Janusz M Bujnicki, Trushar R Patel, Sean A McKenna
Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2α and attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem...
2017: PloS One
https://www.readbyqxmd.com/read/29053189/pilot-screening-study-of-targeted-genetic-polymorphisms-for-association-with-seasonal-influenza-hospital-admission
#2
Tonia C Carter, Scott J Hebbring, Jixia Liu, Jonathan D Mosley, Christian M Shaffer, Lynn C Ivacic, Sarah Kopitzke, Elisha L Stefanski, Rob Strenn, Maria E Sundaram, Jennifer Meece, Murray H Brilliant, Jill M Ferdinands, Edward A Belongia
Host response to influenza is highly variable, suggesting a potential role of host genetic variation. To investigate the host genetics of severe influenza in a targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune response genes were evaluated for association with seasonal influenza hospitalization in an adult study population with European ancestry. SNP allele and genotype frequencies were compared between hospitalized influenza patients (cases) and population controls in a case-control study that included a discovery group (26 cases and 993 controls) and two independent, validation groups (one with 84 cases and 4,076 controls; the other with 128 cases and 9,187 controls)...
October 20, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29052304/immunotherapy-for-hepatitis-b-in-the-direct-acting-anti-viral-era-reevaluating-the-thymosin-%C3%AE-1-efficacy-trials-in-light-of-a-combination-therapy-approach
#3
Paul H Naylor, Milton G Mutchnick
Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as α-Interferon and thymosin α1 can, in select patients, result in elimination of both HBsAg and HBeAg...
October 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29052054/suppression-of-the-toll-like-receptor-7-dependent-type-i-interferon-production-pathway-by-autophagy-resulting-from-enterovirus-71-and-coxsackievirus-a16-infections-facilitates-their-replication
#4
Jie Song, Yajie Hu, Jiaqi Li, Huiwen Zheng, Jingjing Wang, Lei Guo, Haijng Shi, Longding Liu
Toll-like receptors (TLRs) act as molecular sentinels, detecting invading viral pathogens and triggering host innate immune responses, including autophagy. However, many viruses have evolved a series of strategies to manipulate autophagy for their own benefit. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16), as the primary agents causing hand, foot and mouth disease (HFMD), can induce autophagy leading to their replication. Therefore, the objective of this study was to investigate whether enhanced viral replication caused by autophagy in EV71 and CA16 infections was associated with a TLR-related signaling pathway...
October 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29046460/myeloid-dendritic-cells-repress-human-cytomegalovirus-gene-expression-and-spread-by-releasing-interferon-unrelated-soluble-antiviral-factors
#5
Bahram Kasmapour, Tobias Kubsch, Ulfert Rand, Britta Eiz-Vesper, Martin Messerle, Florian W R Vondran, Bettina Wiegmann, Axel Haverich, Luka Cicin-Sain
Cytomegalovirus (CMV) is a beta-herpesvirus that latently infects most adult humans worldwide and is a major cause of morbidity and mortality in immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in precursors of myeloid-lineage, leukocytes and monocytes, which give raise to macrophages and dendritic cells. We report here that human monocyte derived DCs (mo-DC) suppress HCMV infection in coculture with infected fibroblasts target cells in an effector-to-target-ratio dependent manner. Intriguingly, optimal activation of mo-DC was achieved in coculture conditions, not by their direct infection with HCMV, implying that mo-DC may recognize unique molecular patterns on, or within, infected fibroblasts...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046456/viperin-targets-flavivirus-virulence-by-inducing-assembly-of-non-infectious-capsid-particles
#6
Kirstin Vonderstein, Emma Nilsson, Philipp Hubel, Lars Nygård Skalman, Arunkumar Upadhyay, Jenny Pasto, Andreas Pichlmair, Richard Lundmark, Anna K Överby
Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. Here we describe a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly, and involves release of malfunctional membrane associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad spectrum antiviral interferon stimulated gene...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046453/murine-hepatitis-virus-nsp14-exoribonuclease-activity-is-required-for-resistance-to-innate-immunity
#7
James Brett Case, Yize Li, Ruth Elliott, Xiaotao Lu, Kevin W Graepel, Nicole R Sexton, Everett Clinton Smith, Susan R Weiss, Mark R Denison
Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that counteract the host innate immune response to facilitate efficient viral replication. CoV non-structural protein 14 (nsp14) encodes 3' -to-5' exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade dsRNA replication intermediates...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046449/gga-mir-130b-suppresses-infectious-bursal-disease-virus-replication-via-targeting-the-viral-genome-and-cellular-socs5
#8
Mengjiao Fu, Bin Wang, Xiang Chen, Zhiyuan He, Yongqiang Wang, Xiaoqi Li, Hong Cao, Shijun J Zheng
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post transcriptionally through silencing or degrading its targets, playing important roles in immune response. However, the role of miRNAs in host response against infectious bursal disease virus (IBDV) infection is not clear. In this study, we show that the expression of a series of miRNAs was significantly altered in DF-1 cells after infectious bursal disease virus (IBDV) infection. We found that gga-miR-130b inhibited IBDV replication via targeting the specific sequence of IBDV segment A and enhanced the expression of IFN-β by targeting Suppressors of Cytokine Signaling 5(SOCS5) in host cells...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046350/host-transcription-factor-speckled-110kda-sp110-a-nuclear-body-protein-is-hijacked-by-hepatitis-b-virus-protein-x-for-viral-persistence
#9
Isha Sengupta, Dipanwita Das, Shivaram Prasad Singh, Runu Chakravarty, Chandrima Das
Promyelocytic leukemia nuclear bodies (PMLNB) are sub-nuclear organelles which are the hub of numerous proteins. DNA/RNA viruses often hijack cellular-factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29045741/respiratory-syncytial-virus-genotypes-host-immune-profiles-and-disease-severity-in-young-children-hospitalized-with-bronchiolitis
#10
Rosa Rodriguez-Fernandez, Lorena I Tapia, Chin-Fen Yang, Juan Pablo Torres, Susana Chavez-Bueno, Carla Garcia, Lisa M Jaramillo, Melissa Moore-Clingenpeel, Hasan S Jafri, Mark E Peeples, Pedro A Piedra, Octavio Ramilo, Asuncion Mejias
Background: Data on how RSV genotypes influence disease severity and host immune responses is limited. We characterized the genetic variability of RSV during five seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on disease severity and host transcriptional profiles. Methods: Prospective, observational study including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing and genotyping, and blood samples for transcriptome analyses were obtained within 24h of hospitalization...
October 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29045448/interferon-free-therapy-with-direct-acting-antivirals-for-hcv-hiv-1-co-infected-japanese-patients-with-inherited-bleeding-disorders
#11
Haruka Uemura, Kunihisa Tsukada, Daisuke Mizushima, Takahiro Aoki, Koji Watanabe, Ei Kinai, Katsuji Teruya, Hiroyuki Gatanaga, Yoshimi Kikuchi, Masaya Sugiyama, Masashi Mizokami, Shinichi Oka
INTRODUCTION: Almost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs. METHODS: We conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1...
2017: PloS One
https://www.readbyqxmd.com/read/29045416/neonatal-immune-response-to-rhinovirus-a16-has-diminished-dendritic-cell-function-and-increased-b-cell-activation
#12
Amanda Barlow-Anacker, Yury Bochkov, James Gern, Christine M Seroogy
BACKGROUND: Rhinovirus infections during infancy account for the majority of respiratory illness health care utilization and are an associated risk factor for subsequent development of allergic asthma. Neonatal type I interferon production is diminished compared to adults after stimulation with TLR agonists. However, broad profiling of immune cell responses to infectious rhinovirus has not been undertaken and we hypothesized that additional immune differences can be identified in neonates...
2017: PloS One
https://www.readbyqxmd.com/read/29042669/rna-editing-by-adar1-regulates-innate-and-antiviral-immune-functions-in-primary-macrophages
#13
Maria Pujantell, Eva Riveira-Muñoz, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Guillem Sirera, Teresa Puig, Cristina Ramirez, Bonaventura Clotet, José A Esté, Ester Ballana
ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042578/%C3%AE-defensin-1-expression-in-hcv-infected-liver-liver-cancer-an-important-role-in-protecting-hcv-progression-and-liver-cancer-development
#14
Yue-Ming Ling, Jin-Yu Chen, Libin Guo, Chen-Yi Wang, Wen-Ting Tan, Qing Wen, Shu-Dong Zhang, Guo-Hong Deng, Yao Lin, Hang Fai Kwok
β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29040989/hepatocellular-carcinoma-after-achievement-of-sustained-viral-response-with-daclatasvir-and-asunaprevir-in-patients-with-chronic-hepatitis-c-virus-infection
#15
Hiroshi Ida, Satoru Hagiwara, Masashi Kono, Tomohiro Minami, Hirokazu Chishina, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Yasunori Minami, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
BACKGROUND: Interferon-based antiviral therapies against hepatitis C virus (HCV) infection have been shown to reduce the incidence of hepatocellular carcinoma (HCC) in patients with sustained viral response (SVR). Recently, direct-acting antivirals (DAAs) have been proven to be much more effective in achieving SVR than interferon-based therapies. However, whether DAAs can efficiently prevent the occurrence of HCC after SVR remains controversial. To clarify this issue, we analyzed the clinical features of patients in whom HCC developed after achievement of SVR with DAAs for chronic HCV infection...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29040311/putative-endogenous-filovirus-vp35-like-protein-potentially-functions-as-an-ifn-antagonist-but-not-a-polymerase-cofactor
#16
Tatsunari Kondoh, Rashid Manzoor, Naganori Nao, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Makoto Kuroda, Keita Matsuno, Daisuke Fujikura, Masahiro Kajihara, Reiko Yoshida, Manabu Igarashi, Ayato Takada
It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication...
2017: PloS One
https://www.readbyqxmd.com/read/29037975/modular-cell-based-platform-for-high-throughput-identification-of-compounds-that-inhibit-a-viral-interferon-antagonist-of-choice
#17
Andri Vasou, Christina Paulus, Janina Narloch, Zoe O Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E Randall, Catherine S Adamson
Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29035002/short-term-risk-of-hepatocellular-carcinoma-after-hepatitis-c-virus-eradication-following-direct-acting-anti-viral-treatment
#18
E Ogawa, N Furusyo, H Nomura, K Dohmen, N Higashi, K Takahashi, A Kawano, K Azuma, T Satoh, M Nakamuta, T Koyanagi, M Kato, S Shimoda, E Kajiwara, J Hayashi
BACKGROUND: With the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR). AIM: To evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS: This large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523)...
October 16, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29033947/interferon-%C3%AE-s-front-line-guardians-of-immunity-and-homeostasis-in-the-respiratory-tract
#19
REVIEW
Evangelos Andreakos, Maria Salagianni, Ioanna E Galani, Ourania Koltsida
Type III interferons (IFNs), also termed lambda IFNs (IFNλs) or interleukins-28/29, constitute a new addition to the IFN family. They are induced upon infection and are particularly abundant at barrier surfaces, such as the respiratory and gastrointestinal tracts. Although they signal through a unique heterodimeric receptor complex comprising IFNLR1 and IL10RB, they activate a downstream signaling pathway remarkably similar to that of type I IFNs and share many functions with them. Yet, they also have important differences which are only now starting to unfold...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033943/human-immunodeficiency-virus-1-and-type-i-interferons-where-sex-makes-a-difference
#20
REVIEW
Susanne Maria Ziegler, Marcus Altfeld
The human immunodeficiency virus (HIV)-1 epidemic continues to represent a global health problem that is over-proportionally affecting women from sub-Saharan Africa. Besides social and environmental factors, the modulation of immunological pathways by sex hormones and gene dosage effects of X chromosomal-encoded genes have been suggested to lead to differential outcomes in HIV-1 disease. Women present with lower HIV-1 loads early in infection. However, the progression to AIDS for the same level of viremia is faster in women than in men...
2017: Frontiers in Immunology
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