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Immunopathology of viral

Roberta Rovito, Marjolein J Korndewal, Menno C van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C M Kroes, Anton W Langerak, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Mohanraj Manangeeswaran, Derek D C Ireland, Daniela Verthelyi
The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice...
November 2016: PLoS Pathogens
Sara Verpoest, Brigitte Cay, Herman Favoreel, Nick De Regge
: Severity of clinical symptoms induced by pseudorabies virus (PRV) infection of its natural host is inversely related with the age of the pig. During this study, pigs of 2- and 15-week-old were inoculated with the PRV strain NIA3. This resulted in important clinical disease although associated morbidity and mortality were lower in older pigs. qPCR analysis of viral DNA in different organs confirmed the general knowledge on PRV pathogenesis. Several new findings and potential explanations for the observed age-dependent differences in virulence however sorted from the study of viral and cytokine mRNA expression at important sites of neuropathogenesis...
November 16, 2016: Journal of Virology
Yu Hu, Ji Hyung Kim, Kangmin He, Qi Wan, Jessica Kim, Melanie Flach, Tom Kirchhausen, Andrea Vortkamp, Florian Winau
In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes...
November 14, 2016: Journal of Experimental Medicine
Namir Shaabani, Vikas Duhan, Vishal Khairnar, Asmae Gassa, Rita Ferrer-Tur, Dieter Häussinger, Mike Recher, Gennadiy Zelinskyy, Jia Liu, Ulf Dittmer, Mirko Trilling, Stefanie Scheu, Cornelia Hardt, Philipp A Lang, Nadine Honke, Karl S Lang
Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8(+) T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169(+) macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169(+) macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus...
November 3, 2016: Cell Death & Disease
Jenny W Che, Keith A Daniels, Liisa K Selin, Raymond M Welsh
: One's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. This can occur after acute viral infections, such as lymphocytic choriomeningitis virus (LCMV) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. In this study, murine cytomegalovirus (MCMV) was used as a persistent infection model to study heterologous immunity with LCMV...
November 2, 2016: Journal of Virology
Günther Schönrich, Martin J Raftery
Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils...
2016: Frontiers in Immunology
May Griffith, Mohammad M Islam, Joel Edin, Georgia Papapavlou, Oleksiy Buznyk, Hirak K Patra
Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation...
2016: Frontiers in Bioengineering and Biotechnology
Anthony Brown, John S Halliday, Leo Swadling, Richie G Madden, Richard Bendall, Jeremy G Hunter, James Maggs, Peter Simmonds, Donald B Smith, Louisa Vine, Cara McLaughlin, Jane Collier, David Bonsall, Katie Jeffery, Susanna Dunachie, Paul Klenerman, Jacques Izopet, Nassim Kamar, Harry R Dalton, Eleanor Barnes
: The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ekaterina P Koroleva, Yang-Xin Fu, Alexei V Tumanov
Lymphotoxin (LT) is a member of the tumor necrosis factor (TNF) superfamily of cytokines which serves multiple functions, including the control of lymphoid organ development and maintenance, as well as regulation of inflammation and autoimmunity. Although the role of LT in organogenesis and maintenance of lymphoid organs is well established, the contribution of LT pathway to homeostasis of lymphoid organs during the immune response to pathogens is less understood. In this review, we highlight recent advances on the role of LT pathway in antiviral immune responses...
September 9, 2016: Cytokine
Ann-Kathrin Uhde, Vanessa Herder, Muhammad Akram Khan, Malgorzata Ciurkiewicz, Dirk Schaudien, René Teich, Stefan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease...
2016: PloS One
Jessica R Spengler, Kerry J Lavender, Cynthia Martellaro, Aaron Carmody, Andreas Kurth, James G Keck, Greg Saturday, Dana P Scott, Stuart T Nichol, Kim J Hasenkrug, Christina F Spiropoulou, Heinz Feldmann, Joseph Prescott
The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34(+) stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation...
October 15, 2016: Journal of Infectious Diseases
Martijn J Schuijs, Susanne Hartmann, Murray E Selkirk, Luke B Roberts, Peter J M Openshaw, Corinna Schnoeller
Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis...
2016: PloS One
Stephanie Johnstone, Jekaterina Barsova, Isabel Campos, Arthur R Frampton
Equine herpesvirus myeloencephalopathy (EHM), a disease caused by equine herpesvirus type 1 (EHV-1), is characterized by severe inflammation, thrombosis, and hypoxia in central nervous system (CNS) endothelial cells, which can result in a spectrum of clinical signs including urinary incontinence, ataxia, and paralysis. Strains of EHV-1 that contain a single point mutation within the viral DNA polymerase (nucleotide A2254>G2254: amino acid N752→D752) are isolated from EHM afflicted horses at higher frequencies than EHV-1 strains that do not harbor this mutation...
August 30, 2016: Veterinary Microbiology
Sophia Davidson, Teresa M McCabe, Stefania Crotta, Hans Henrik Gad, Edith M Hessel, Soren Beinke, Rune Hartmann, Andreas Wack
Influenza A virus (IAV)-induced severe disease is characterized by infected lung epithelia, robust inflammatory responses and acute lung injury. Since type I interferon (IFNαβ) and type III interferon (IFNλ) are potent antiviral cytokines with immunomodulatory potential, we assessed their efficacy as IAV treatments. IFNλ treatment of IAV-infected Mx1-positive mice lowered viral load and protected from disease. IFNα treatment also restricted IAV replication but exacerbated disease. IFNα treatment increased pulmonary proinflammatory cytokine secretion, innate cell recruitment and epithelial cell death, unlike IFNλ-treatment...
September 1, 2016: EMBO Molecular Medicine
Amanda L Gill, Samantha A Green, Shahed Abdullah, Cecile Le Saout, Stefania Pittaluga, Hui Chen, Refika Turnier, Jeffrey Lifson, Steven Godin, Jing Qin, Michael C Sneller, Jean-Marie Cuillerot, Helen Sabzevari, H Clifford Lane, Marta Catalfamo
OBJECTIVE: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target...
October 23, 2016: AIDS
Pushpa Pandiyan, Souheil-Antoine Younes, Susan Pereira Ribeiro, Aarthi Talla, David McDonald, Natarajan Bhaskaran, Alan D Levine, Aaron Weinberg, Rafick P Sekaly
Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues...
2016: Frontiers in Immunology
Jia Xue, Xiaoxu Fan, Jing Yu, Shouping Zhang, Jin Xiao, Yanxin Hu, Ming Wang
Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1...
2016: Frontiers in Microbiology
Eui-Cheol Shin, Pil Soo Sung, Su-Hyung Park
Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection...
August 2016: Nature Reviews. Immunology
Myung-Soo Choi, Jinyuk Heo, Chae-Min Yi, Junsu Ban, Noh-Jin Lee, Na-Rae Lee, Sang Won Kim, Nam-Jung Kim, Kyung-Soo Inn
Respiratory syncytial virus (RSV) and influenza A virus are leading causes of acute lower respiratory infectious disease. Respiratory diseases caused by RSV and influenza A virus result in serious economic burden and life-threatening disease for immunocompromised people. With the revelation that p38 mitogen-activated protein kinase (MAPK) activity in host cells is crucial for infection and replication of RSV and influenza A virus, inhibition of p38 MAPK activity has been suggested as a potential antiviral therapeutic strategy...
August 26, 2016: Biochemical and Biophysical Research Communications
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