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Pathogenesis of viral infection of the lungs

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https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#1
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29329577/respiratory-explants-as-a-model-to-investigate-early-events-of-contagious-bovine-pleuropneumonia-infection
#2
Giovanni Di Teodoro, Giuseppe Marruchella, Andrea Di Provvido, Gianluca Orsini, Gaetano Federico Ronchi, Anna Rita D'Angelo, Nicola D'Alterio, Flavio Sacchini, Massimo Scacchia
Contagious bovine pleuropneumonia (CBPP) is a severe disease caused by Mycoplasma mycoides subsp. mycoides (Mmm). Knowledge on CBPP pathogenesis is fragmented and hampered by the limited availability of laboratory animal and in vitro models of investigation. The purpose of the present study is to assess respiratory explants as useful tools to study the early stages of CBPP. Explants were obtained from trachea, bronchi and lungs of slaughtered cattle, tested negative for Mycoplasma spp. and for the major bacterial and viral respiratory pathogens...
January 12, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29321591/respiratory-syncytial-virus-infection-changes-cargo-composition-of-exosome-released-from-airway-epithelial-cells
#3
Harendra Singh Chahar, Tiziana Corsello, Andrzej S Kudlicki, Narayana Komaravelli, Antonella Casola
Exosomes are microvesicles known to carry biologically active molecules, including RNA, DNA and proteins. Viral infections can induce profound changes in exosome composition, and exosomes have been implicated in viral transmission and pathogenesis. No information is current available regarding exosome composition and function during infection with Respiratory Syncytial Virus (RSV), the most important cause of lower respiratory tract infections in children. In this study, we characterized exosomes released from RSV-infected lung carcinoma-derived A549 cells...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29282312/nlrp12-mediates-adverse-neutrophil-recruitment-during-influenza-virus-infection
#4
Emma E Hornick, Balaji Banoth, Ann M Miller, Zeb R Zacharias, Nidhi Jain, Mary E Wilson, Katherine N Gibson-Corley, Kevin L Legge, Gail A Bishop, Fayyaz S Sutterwala, Suzanne L Cassel
Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29241072/combined-efficacy-of-oseltamivir-isoprinosine-and-ellagic-acid-in-influenza-a-h3n2-infected-mice
#5
Elitsa L Pavlova, Lora S Simeonova, Galina A Gegova
Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug - oseltamivir (OS), 500mg/kg/day of the immune modulator - isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice...
December 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29237287/early-sites-of-virus-replication-after-oral-sivmac251-infection-of-infant-macaques-implications-for-pathogenesis
#6
Angela Amedee, Bonnie Phillips, Kara Jensen, Spencer Robichaux, Nedra Lacour, Mark Burke, Michael Piatak, Jeffrey Lifson, Pamela A Kozlowski, Koen K A Van Rompay, Kristina De Paris
Despite optimization of preventative measures for vertical HIV-1 transmission, daily roughly 400 infants become HIV infected, most of them via breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified viral RNA and DNA in oral, intestinal and systemic tissues of 15 infant macaques within 48-96 hours after oral SIVmac251 exposure. SIV DNA was detected as early as 48 hours, whereas SIV RNA was typically detected at later time points (72-96 hours)...
December 14, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29175108/nonstructural-protein-2a-modulates-replication-and-virulence-of-enterovirus-71
#7
Chun Li, Qiao Qiao, Shu-Bin Hao, Zhen Dong, Li Zhao, Jing Ji, Zhi-Yu Wang, Hong-Ling Wen
Enterovirus 71 (EV71) can cause hand, foot, and mouth disease in children, and severe infections can induce neurological complications and even death. However, the pathogenesis of EV71 remains unknown. The 2A proteinase (2Apro) of EV71 plays an important role in segmenting the precursor polyprotein during viral replication, inhibiting host protein synthesis, and evading innate immunity. This study was to determine the function of EV71 2Apro in replication and virulence. A chimeric strain (SDLY 107-2A-1) was recombined by replacing 2Apro of a severe strain (SDLY107) with that of a mild strain (SDLY1) based on an infectious cDNA clone...
November 21, 2017: Virus Research
https://www.readbyqxmd.com/read/29140992/transcriptome-profile-of-lung-dendritic-cells-after-in-vitro-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-infection
#8
Maren Julia Pröll, Christiane Neuhoff, Karl Schellander, Muhammad Jasim Uddin, Mehmet Ulas Cinar, Sudeep Sahadevan, Xueqi Qu, Md Aminul Islam, Mikhael Poirier, Marcel A Müller, Christian Drosten, Dawit Tesfaye, Ernst Tholen, Christine Große-Brinkhaus
The porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that leads to high financial and production losses in the global swine industry. The pathogenesis of this disease is dependent on a multitude of factors, and its control remains problematic. The immune system generally defends against infectious diseases, especially dendritic cells (DCs), which play a crucial role in the activation of the immune response after viral infections. However, the understanding of the immune response and the genetic impact on the immune response to PRRS virus (PRRSV) remains incomplete...
2017: PloS One
https://www.readbyqxmd.com/read/29105740/protease-activated-receptor-1-inhibition-protects-mice-against-thrombin-dependent-respiratory-syncytial-virus-and-human-metapneumovirus-infections
#9
Vuong Ba Lê, Béatrice Riteau, Marie-Christine Alessi, Christian Couture, Martine Jandrot-Perrus, Chantal Rhéaume, Marie-Ève Hamelin, Guy Boivin
BACKGROUND AND PURPOSE: Protease-activated receptor 1 (PAR1) has been demonstrated to be involved in the pathogenesis of viral diseases. However, its role remains controversial. The goal of our study was to investigate the contribution of PAR1 to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections. EXPERIMENTAL APPROACH: Pharmacological approaches were used to investigate the role of PAR1 during RSV and hMPV, in vitro using epithelial A549 cells and in vivo using a mouse model of virus infections...
November 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29100887/a-pharmacologically-immunosuppressed-mouse-model-for-assessing-influenza-b-virus-pathogenicity-and-oseltamivir-treatment
#10
Bindumadhav M Marathe, Heba H Mostafa, Peter Vogel, Philippe Noriel Q Pascua, Jeremy C Jones, Charles J Russell, Richard J Webby, Elena A Govorkova
Immunocompromised patients are highly susceptible to influenza virus infections. Although neuraminidase inhibitor (NAI) therapy has proved effective in these patients, the treatment regimens require optimization, which can be partly addressed via animal models. Here, we describe a pharmacologically immunosuppressed mouse model for studying the pathogenesis of influenza B viruses and evaluating the efficacy of antiviral treatment. We modeled clinical regimens for dexamethasone and cyclophosphamide to immunosuppress BALB/c mice that were then inoculated with B/Phuket/3073/2013 (Yamagata lineage) or B/Brisbane/60/2008 (BR/08, Victoria lineage) virus...
October 31, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29046461/human-embryonic-stem-cell-derived-neurons-are-highly-permissive-for-varicella-zoster-virus-lytic-infection
#11
Tomohiko Sadaoka, Cindi L Schwartz, Labchan Rajbhandari, Arun Venkatesan, Jeffrey I Cohen
Varicella-zoster virus (VZV) is highly cell-associated when grown in culture and has a much higher (4,000 to 20,000-fold increased) particle-to-plaque forming unit (PFU) ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo, in which the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrate that neurons are nearly 100 times more permissive for WT VZV infection than very early passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29038764/pulmonary-transcriptomic-responses-indicate-a-dual-role-of-inflammation-in-pneumonia-development-and-viral-clearance-during-2009-pandemic-influenza-infection
#12
Raquel Almansa, Pamela Martínez-Orellana, Lucía Rico, Verónica Iglesias, Alicia Ortega, Beatriz Vidaña, Jorge Martínez, Ana Expósito, María Montoya, Jesús F Bermejo-Martin
BACKGROUND: The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed. METHODS: A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection...
2017: PeerJ
https://www.readbyqxmd.com/read/28930978/influenza-a-virus-studies-in-a-mouse-model-of-infection
#13
Laura Rodriguez, Aitor Nogales, Luis Martínez-Sobrido
Influenza viruses cause over 500,000 deaths worldwide(1) and are associated with an annual cost of 12 - 14 billion USD in the United States alone considering direct medical and hospitalization expenses and work absenteeism(2). Animal models are crucial in Influenza A virus (IAV) studies to evaluate viral pathogenesis, host-pathogen interactions, immune responses, and the efficacy of current and/or novel vaccine approaches as well as antivirals. Mice are an advantageous small animal model because their immune system is evolutionarily similar to that found in humans, they are available from commercial vendors as genetically identical subjects, there are multiple strains that can be exploited to evaluate the genetic basis of infections, and they are relatively inexpensive and easy to manipulate...
September 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28889999/humoral-immune-responses-during-asthma-and-influenza-co-morbidity-in-mice
#14
Laura A Doorley, Kim S LeMessurier, Amy R Iverson, Maneesha Palipane, Amali E Samarasinghe
Humoral immunity serve dual functions of direct pathogen neutralization and enhancement of leukocyte function. Antibody classes are determined by antigen triggers, and the resulting antibodies can contribute to disease pathogenesis and host defense. Although asthma and influenza are immunologically distinct diseases, since we have found that allergic asthma exacerbation promotes antiviral host responses to influenza A virus, we hypothesized that humoral immunity may contribute to allergic host protection during influenza...
December 2017: Immunobiology
https://www.readbyqxmd.com/read/28865344/heartland-virus-infection-in-hamsters-deficient-in-type-i-interferon-signaling-protracted-disease-course-ameliorated-by-favipiravir
#15
Jonna B Westover, Johanna D Rigas, Arnaud J Van Wettere, Rong Li, Brady T Hickerson, Kie-Hoon Jung, Jinxin Miao, Erin S Reynolds, Bettina L Conrad, Skot Nielson, Yousuke Furuta, Saravanan Thangamani, Zhongde Wang, Brian B Gowen
Heartland virus (HRTV) is an emerging tick-borne virus (Bunyaviridae, Phlebovirus) that has caused sporadic cases of human disease in several central and mid-eastern states of America. Animal models of HRTV disease are needed to gain insights into viral pathogenesis and advancing antiviral drug development. Presence of clinical disease following HRTV challenge in hamsters deficient in STAT2 function underscores the important role played by type I interferon-induced antiviral responses. However, the recovery of most of the infected animals suggests that other mechanisms to control infection and limit disease offer substantial protection...
November 2017: Virology
https://www.readbyqxmd.com/read/28858723/epigallocatechin-3-gallate-inhibits-tlr4-signaling-through-the-67-kda-laminin-receptor-and-effectively-alleviates-acute-lung-injury-induced-by-h9n2-swine-influenza-virus
#16
Ming-Ju Xu, Bao-Jian Liu, Cun-Lian Wang, Guo-Hua Wang, Yong Tian, Shao-Hua Wang, Jun Li, Pei-Yao Li, Rui-Hua Zhang, Dong Wei, Shu-Fei Tian, Tong Xu
Epigallocatechin-3-gallate (EGCG) was found to inhibit the Toll-like receptor 4 (TLR4) pathway involved in influenza virus pathogenesis. Here, the effect of EGCG on TLR4 in an H9N2 virus-induced acute lung injury mouse model was investigated. BALB/c mice were inoculated intranasally with A/Swine/Hebei/108/2002 (H9N2) virus or noninfectious allantoic fluid, and treated with EGCG and E5564 or normal saline orally for 5 consecutive days. PMVECs were treated with EGCG or anti-67kDa laminin receptor (LR). Lung physiopathology, inflammation, oxidative stress, viral replication, and TLR4/NF-κB/Toll-interacting protein (Tollip) pathway in lung tissue and/or PMVECs were investigated...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28858401/histopathology-of-middle-east-respiratory-syndrome-coronovirus-mers-cov-infection-clinicopathological-and-ultrastructural-study
#17
Khaled O Alsaad, Ali H Hajeer, Mohammed Al Balwi, Mohammed Al Moaiqel, Nourah Al Oudah, Abdulaziz Al Ajlan, Sameera AlJohani, Sami Alsolamy, Giamal E Gmati, Hanan Balkhy, Hamdan H Al-Jahdali, Salim A Baharoon, Yaseen M Arabi
AIMS: The pathogenesis, viral localization and histopathological features of Middle East Respiratory Syndrome - Coronavirus (MERS-CoV) in human are not sufficiently described. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. METHODS AND RESULTS: We analyzed the postmortem histopathological findings and investigated viral particles localization in the pulmonary and extra-pulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T-cell lymphoma, who acquired MERS-CoV infection...
August 31, 2017: Histopathology
https://www.readbyqxmd.com/read/28840816/a-persistently-infecting-coronavirus-in-hibernating-myotis-lucifugus-the-north-american-little-brown-bat
#18
Sonu Subudhi, Noreen Rapin, Trent K Bollinger, Janet E Hill, Michael E Donaldson, Christina M Davy, Lisa Warnecke, James M Turner, Christopher J Kyle, Craig K R Willis, Vikram Misra
Bats are important reservoir hosts for emerging viruses, including coronaviruses that cause diseases in people. Although there have been several studies on the pathogenesis of coronaviruses in humans and surrogate animals, there is little information on the interactions of these viruses with their natural bat hosts. We detected a coronavirus in the intestines of 53/174 hibernating little brown bats (Myotis lucifugus), as well as in the lungs of some of these individuals. Interestingly, the presence of the virus was not accompanied by overt inflammation...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28827121/a-scid-mouse-human-lung-xenograft-model-of-varicella-zoster-virus-infection
#19
Wei Wang, Dequan Pan, Wenkun Fu, Linli Cai, Jianghui Ye, Jian Liu, Che Liu, Xiumin Huang, Yanzhen Lin, Ningshao Xia, Tong Cheng, Hua Zhu
Varicella pneumonia is one of the most serious, potentially life-threatening complications of primary varicella-zoster virus (VZV) infection in adults and immunocompromised individuals. However, studies on the lung pathogenesis of VZV infection as well as development and testing of antivirals have long been hindered by limited access to clinical samples and a lack of suitable animal models. In this study, we report for the first time the use of human lung xenografts in SCID mice for investigating VZV infection...
August 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28812530/feline-herpesvirus-pneumonia-investigations-into-the-pathogenesis
#20
Josep Maria Monne Rodriguez, Gail Leeming, Kernt Köhler, Anja Kipar
Feline herpesvirus type 1 (FeHV-1) is one of the etiological agents of feline respiratory disease. FeHV-1 is an epitheliotropic and cytopathic virus that mainly causes rhinitis and conjunctivitis, although pneumonia is also occasionally seen. In this study, the authors investigated the pathogenesis of FeHV-1-associated pneumonia, comparing natural cases with viral infection of tracheal ring and cell cultures in vitro, using histology, immunohistology, double immunofluorescence, and transmission electron microscopy as investigative tools...
January 1, 2017: Veterinary Pathology
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