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Pathogenesis of viral infection of the lungs

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https://www.readbyqxmd.com/read/28282445/endothelial-cell-tropism-is-a-determinant-of-h5n1-pathogenesis-in-mammalian-species
#1
Smanla Tundup, Matheswaran Kandasamy, Jasmine T Perez, Nacho Mena, John Steel, Tamas Nagy, Randy A Albrecht, Balaji Manicassamy
The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown. Here, we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species. We engineered H5N1 viruses with restricted cell tropism through the exploitation of cell type-specific microRNA expression by incorporating microRNA target sites into the viral genome. Restriction of H5N1 replication in endothelial cells via miR-126 ameliorated disease symptoms, prevented systemic viral spread and limited mortality, despite showing similar levels of peak viral replication in the lungs as compared to control virus-infected mice...
March 10, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28279829/tissue-tropism-of-saint-louis-encephalitis-virus-histopathology-triggered-by-epidemic-and-non-epidemic-strains-isolated-in-argentina
#2
María Elisa Rivarola, Guillermo Albrieu-Llinás, María Belén Pisano, Laura Beatriz Tauro, Melisa Gorosito-Serrán, Cristian Gabriel Beccaria, Luis Adrián Díaz, Ana Vázquez, Agustín Quaglia, Cristina López, Lorena Spinsanti, Adriana Gruppi, Marta Silvia Contigiani
Saint Louis encephalitis virus (SLEV) reemerged in South America, and caused encephalitis outbreaks at the beginning of the 21st century. To enhance our knowledge about SLEV virulence, we performed comparative pathogenesis studies in Swiss albino mice inoculated with two different variants, the epidemic strain CbaAr-4005 and the non-epidemic strain CorAn-9275. Only the infection of mice with SLEV strain CbaAr-4005 resulted in high viremia, invasion of peripheral tissues including the lungs, kidney, and spleen, and viral neuroinvasion...
March 6, 2017: Virology
https://www.readbyqxmd.com/read/28262742/il-6-ameliorates-acute-lung-injury-in-influenza-virus-infection
#3
Mei-Lin Yang, Chung-Teng Wang, Shiu-Ju Yang, Chia-Hsing Leu, Shun-Hua Chen, Chao-Liang Wu, Ai-Li Shiau
Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250128/pathology-in-permissive-syrian-hamsters-after-infection-with-human-adenovirus-is-the-result-of-virus-replication-hadv-c6-replicates-more-and-causes-more-pathology-than-hadv-c5
#4
Ann E Tollefson, Baoling Ying, Jacqueline F Spencer, John E Sagartz, William S M Wold, Karoly Toth
Syrian hamsters are permissive for the replication of species C human adenoviruses. The virus replicates to high titers in the liver of these animals after intravenous infection, while respiratory infection results in virus replication in the lung. Here we show that two types belonging to species C, HAdV-C5 and HAdV-C6, replicate to a significantly different extent and cause pathology with significantly different severity, with HAdV-C6 replicating better and inducing more severe and more widespread lesions...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250116/a-neonatal-murine-model-of-coxsackievirus-a6-infection-for-evaluation-of-antiviral-and-vaccine-efficacy
#5
Zhenjie Zhang, Zhaopeng Dong, Qingjuan Wei, Michael J Carr, Juan Li, Shujun Ding, Yigang Tong, Dong Li, Weifeng Shi
Hand, foot and mouth disease (HFMD) is a global health concern. Family Picornaviridae members, particularly enterovirus 71 (EVA71) and Coxsackievirus A16 (CVA16), are the primary etiological agents of HFMD, however, a third enterovirus A species, CoxsackievirusA6 (CVA6), has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered due to the lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection which was employed to evaluate the antiviral activities of different drugs and the protective efficacies of CVA6-inactivated vaccines...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28242695/genetic-variation-in-chromosome-y-regulates-susceptibility-to-influenza-a-virus-infection
#6
Dimitry N Krementsov, Laure K Case, Oliver Dienz, Abbas Raza, Qian Fang, Jennifer L Ather, Matthew E Poynter, Jonathan E Boyson, Janice Y Bunn, Cory Teuscher
Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism that has been proposed to account for this difference is the immunocompetence handicap model, which posits that the greater infectious disease burden in males is due to testosterone, which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors also may contribute to the sex differences in infectious disease burden...
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28241868/dynamic-changes-in-bronchoalveolar-macrophages-and-cytokines-during-infection-of-pigs-with-a-highly-or-low-pathogenic-genotype-1-prrsv-strain
#7
Patricia Renson, Nicolas Rose, Mireille Le Dimna, Sophie Mahé, André Keranflec'h, Frédéric Paboeuf, Catherine Belloc, Marie-Frédérique Le Potier, Olivier Bourry
Porcine reproductive and respiratory syndrome virus (PRRSV) replicates primarily in pulmonary alveolar macrophages (PAMs) and the resulting lung damage is influenced by strain virulence. To better understand the pathogenesis of PRRSV infection, we performed a longitudinal study of the PAM population and lung cytokines in specific pathogen-free pigs infected either with the highly pathogenic Lena strain or with the low pathogenic Finistere strain in comparison to uninfected pigs. Bronchoalveolar lavage fluid (BALF) and blood were collected to follow viral, cellular and cytokine changes in lung with respect to clinical signs and systemic events...
February 27, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28228284/respiratory-syncytial-virus-infects-regulatory-b-cells-in-human-neonates-via-chemokine-receptor-cx3cr1-and-promotes-lung-disease-severity
#8
Dania Zhivaki, Sébastien Lemoine, Annick Lim, Ahsen Morva, Pierre-Olivier Vidalain, Liliane Schandene, Nicoletta Casartelli, Marie-Anne Rameix-Welti, Pierre-Louis Hervé, Edith Dériaud, Benoit Beitz, Maryline Ripaux-Lefevre, Jordi Miatello, Brigitte Lemercier, Valerie Lorin, Delphyne Descamps, Jenna Fix, Jean-François Eléouët, Sabine Riffault, Olivier Schwartz, Fabrice Porcheray, Françoise Mascart, Hugo Mouquet, Xiaoming Zhang, Pierre Tissières, Richard Lo-Man
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28216251/sars-cov-encoded-small-rnas-contribute-to-infection-associated-lung-pathology
#9
Lucía Morales, Juan Carlos Oliveros, Raúl Fernandez-Delgado, Benjamin Robert tenOever, Luis Enjuanes, Isabel Sola
Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18-22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication...
February 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28179378/the-human-immune-response-to-respiratory-syncytial-virus-infection
#10
REVIEW
Clark D Russell, Stefan A Unger, Marc Walton, Jürgen Schwarze
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8)...
April 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28161961/genome-wide-gene-expression-pattern-underlying-differential-host-response-to-high-or-low-pathogenic-h5n1-avian-influenza-virus-in-ducks
#11
A Kumar, P Vijayakumar, P N Gandhale, P B Ranaware, H Kumar, D D Kulkarni, A A Raut, A Mishra
The differences in the influenza viral pathogenesis observed between different pathogenic strains are associated with distinct properties of virus strains and the host immune responses. In order to determine the differences in the duck immune response against two different pathogenic strains, we studied genome-wide host immune gene response of ducks infected with A/duck/India/02CA10/2011 and A/duck/Tripura/103597/2008 H5N1 viruses using custom-designed microarray. A/duck/India/02CA10/2011 is highly pathogenic virus (HP) to ducks, whereas A/duck/Tripura/103597/2008 is a low pathogenic (LP) virus strain...
February 6, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28159164/respiratory-viral-infections-in-chronic-lung-diseases
#12
REVIEW
Clemente J Britto, Virginia Brady, Seiwon Lee, Charles S Dela Cruz
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression...
March 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28120850/critical-role-of-cxcl4-in-the-lung-pathogenesis-of-influenza-h1n1-respiratory-infection
#13
L Guo, K Feng, Y C Wang, J J Mei, R T Ning, H W Zheng, J J Wang, G S Worthen, X Wang, J Song, Q H Li, L D Liu
Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection...
January 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28115001/host-cell-copper-transporters-ctr1-and-atp7a-are-important-for-influenza-a-virus-replication
#14
Jonathan C Rupp, Manon Locatelli, Alexis Grieser, Andrea Ramos, Patricia J Campbell, Hong Yi, John Steel, Jason L Burkhead, Eric Bortz
BACKGROUND: The essential role of copper in eukaryotic cellular physiology is known, but has not been recognized as important in the context of influenza A virus infection. In this study, we investigated the effect of cellular copper on influenza A virus replication. METHODS: Influenza A/WSN/33 (H1N1) virus growth and macromolecule syntheses were assessed in cultured human lung cells (A549) where the copper concentration of the growth medium was modified, or expression of host genes involved in copper homeostasis was targeted by RNA interference...
January 23, 2017: Virology Journal
https://www.readbyqxmd.com/read/28108632/contribution-of-innate-immune-cells-to-pathogenesis-of-severe-influenza-virus-infection
#15
REVIEW
Suzanne L Cole, Ling-Pei Ho
Influenza A viruses (IAVs) cause respiratory illness of varying severity based on the virus strains, host predisposition and pre-existing immunity. Ultimately, outcome and recovery from infection rely on an effective immune response comprising both innate and adaptive components. The innate immune response provides the first line of defence and is crucial to the outcome of infection. Airway epithelial cells are the first cell type to encounter the virus in the lungs, providing antiviral and chemotactic molecules that shape the ensuing immune response by rapidly recruiting innate effector cells such as NK cells, monocytes and neutrophils...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28108375/the-role-of-pattern-recognition-receptors-in-lung-sarcoidosis
#16
Esmaeil Mortaz, Ian M Adcock, Atefhe Abedini, Arda Kiani, Mehdi Kazempour-Dizaji, Masoud Movassaghi, Johan Garssen
Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs)...
January 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28105854/t-705-favipiravir-suppresses-tumor-necrosis-factor-%C3%AE-production-in-response-to-influenza-virus-infection-a-beneficial-feature-of-t-705-as-an-anti-influenza-drug
#17
T Tanaka, T Kamiyama, T Daikoku, K Takahashi, N Nomura, M Kurokawa, K Shiraki
Influenza virus infection induces the production of various cytokines, which play important roles in the pathogenesis of infection. Among the cytokines induced by influenza, tumor necrosis factor (TNF)-α production has been correlated with the severity of lung lesions. We investigated the effects of T-705 (Favipiravir, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) on cytokine production due to influenza virus infection in vitro and in vivo, compared with oseltamivir or GS 4071, an active form of oseltamivir. TNF-α production in mouse macrophage-derived P388D1 cells infected with the influenza virus was lower following treatment with T-705 at concentrations of 0...
February 6, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28076422/monoclonal-antibody-against-g-glycoprotein-increases-respiratory-syncytial-virus-clearance-in-vivo-and-prevents-vaccine-enhanced-diseases
#18
Hyo-Jeong Lee, Jeong-Yoon Lee, Min-Hee Park, Joo-Young Kim, Jun Chang
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illness in infants, young children, and the elderly. The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal antibodies (mAbs; 5H6 and 3A5) against G protein core fragment (Gcf), which consisted of amino acid residues 131 to 230 from RSV A2 G protein. Epitope mapping study revealed that 5H6 specifically binds to the G/164-176 peptide that includes conserved sequences shared by both RSV A and B subtypes, and 3A5 binds to the G/190-204 peptide...
2017: PloS One
https://www.readbyqxmd.com/read/28074713/pathogens-patterns-of-pneumonia-and-epidemiologic-risk-factors-associated-with-respiratory-disease-in-recently-weaned-cattle-in-ireland
#19
Gerard M Murray, Simon J More, Dónal Sammin, Mìcheàl J Casey, Máire C McElroy, Rónan G O'Neill, William J Byrne, Bernadette Earley, Tracy A Clegg, Hywel Ball, Colin J Bell, Joseph P Cassidy
We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently...
January 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28069010/nanoparticle-exposure-reactivates-latent-herpesvirus-and-restores-a-signature-of-acute-infection
#20
Christine Sattler, Franco Moritz, Shanze Chen, Beatrix Steer, David Kutschke, Martin Irmler, Johannes Beckers, Oliver Eickelberg, Philippe Schmitt-Kopplin, Heiko Adler, Tobias Stoeger
BACKGROUND: Inhalation of environmental (nano) particles (NP) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. We hypothesized that NP-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage...
January 10, 2017: Particle and Fibre Toxicology
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