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Pathogenesis of viral infection of the lungs

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https://www.readbyqxmd.com/read/27902340/viral-bacterial-interactions-in-the-respiratory-tract
#1
Carla Bellinghausen, Gernot Gu Rohde, Paul Hm Savelkoul, Emiel Fm Wouters, Frank Rm Stassen
In the respiratory tract, viruses and bacteria can interact on multiple levels. It is well known that respiratory viruses, particularly influenza viruses, increase the susceptibility to secondary bacterial infections. Numerous mechanisms, including compromised physical and immunological barriers, and changes in the microenvironment have hereby been shown to contribute to the development of secondary bacterial infections. In contrast, our understanding of how bacteria shape a response to subsequent viral infection is still limited...
October 18, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27892925/a-mouse-model-for-mers-coronavirus-induced-acute-respiratory-distress-syndrome
#2
Adam S Cockrell, Boyd L Yount, Trevor Scobey, Kara Jensen, Madeline Douglas, Anne Beall, Xian-Chun Tang, Wayne A Marasco, Mark T Heise, Ralph S Baric
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV...
November 28, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#3
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825367/involvement-of-the-different-lung-compartments-in-the-pathogenesis-of-ph1n1-influenza-virus-infection-in-ferrets
#4
Beatriz Vidaña, Jorge Martínez, Jaime Martorell, María Montoya, Lorena Córdoba, Mónica Pérez, Natàlia Majó
Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques...
November 8, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27822141/hiv-1-nef-promotes-migration-and-chemokine-synthesis-of-human-basophils-and-mast-cells-through-the-interaction-with-cxcr4
#5
Francesca Wanda Rossi, Nella Prevete, Felice Rivellese, Antonio Lobasso, Filomena Napolitano, Francescopaolo Granata, Carmine Selleri, Amato de Paulis
BACKGROUND: The Nef protein can be detected in plasma of HIV-1-infected patients and plays a role in the pathogenesis of HIV-1. Nef produced during the early stages of infection is fundamental in creating the ideal environment for viral replication, e.g. by reducing the ability of infected cells to induce an immune response. AIM: Based on previous experience showing that both Tat and gp41 of HIV-1 are potent chemotactic factors for basophils and mast cells, and gp120 is a powerful stimulus for the release of histamine and cytokines (IL-4 and IL-13) from basophils, in this study we aimed to verify if the HIV Nef protein can exert some effects on basophils and mast cells purified from healthy volunteers through the interaction with the CXCL12 receptor, CXCR4...
2016: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/27815260/age-and-testosterone-mediate-influenza-pathogenesis-in-male-mice
#6
Landon G Vom Steeg, Meghan S Vermillion, Olivia J Hall, Ornob Alam, Ross McFarland, Haolin Chen, Barry Zirkin, Sabra L Klein
Influenza severity increases with age, with hospitalization and mortality rates during seasonal influenza epidemics being higher in older men than age-matched women. Based on knowledge that with age, circulating testosterone levels decline in males, we hypothesized that reduced testosterone contributes to age-associated increases in influenza severity. A murine model was used to test this hypothesis. As in men, testosterone concentrations were lower in aged (18 months) than young (2 months) male C57BL/6 mice...
November 4, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27814404/enterovirus-d-68-infection-prophylaxis-and-vaccination-in-a-novel-permissive-animal-model-the-cotton-rat-sigmodon-hispidus
#7
Mira C Patel, Wei Wang, Lioubov M Pletneva, Seesandra V Rajagopala, Yi Tan, Tina V Hartert, Marina S Boukhvalova, Stefanie N Vogel, Suman R Das, Jorge C G Blanco
In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus)...
2016: PloS One
https://www.readbyqxmd.com/read/27707929/constitutively-expressed-ifitm3-protein-in-human-pulmonary-endothelial-cells-poses-an-early-infection-block-to-human-influenza-viruses
#8
Xiangjie Sun, Hui Zeng, Amrita Kumar, Jessica A Belser, Taronna R Maines, Terrence M Tumpey
: A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. Here, we found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses...
October 5, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27662546/chronic-lung-disease-in-hiv-infected-children-established-on-antiretroviral-therapy
#9
Jamie Rylance, Grace Mchugh, John Metcalfe, Hilda Mujuru, Kusum Nathoo, Stephanie Wilmore, Sarah Rowland-Jones, Edith Majonga, Katharina Kranzer, Rashida A Ferrand
OBJECTIVE: Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group. DESIGN: A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area...
November 28, 2016: AIDS
https://www.readbyqxmd.com/read/27647909/whole-exome-sequencing-identifies-multiple-loss-of-function-mutations-of-nf-%C3%AE%C2%BAb-pathway-regulators-in-nasopharyngeal-carcinoma
#10
Hong Zheng, Wei Dai, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Rebecca Kan, Bonnie Wing Yan Wong, Merrin Man Long Leong, Mingdan Deng, Tommy Chin Tung Kwok, Jimmy Yu-Wai Chan, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Wai Tong Ng, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Victor Ho-Fun Lee, Ka-On Lam, Chung Kong Kwan, Wing Sum Li, Stephen Yau, Kwok-Wah Chan, Maria Li Lung
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27579026/early-il-1-signaling-promotes-ibalt-induction-after-influenza-virus-infection
#11
Katrijn Neyt, Corine H GeurtsvanKessel, Kim Deswarte, Hamida Hammad, Bart N Lambrecht
Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27560373/interferon-dependent-immunoproteasome-activity-during-mouse-adenovirus-type-1-infection
#12
Mary K McCarthy, Danielle H Malitz, Caitlyn T Molloy, Megan C Procario, Kaitlyn E Greiner, Luna Zhang, Ping Wang, Sharlene M Day, Saul R Powell, Jason B Weinberg
The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner...
November 2016: Virology
https://www.readbyqxmd.com/read/27507829/host-physiologic-changes-induced-by-influenza-a-virus-lead-to-staphylococcus-aureus-biofilm-dispersion-and-transition-from-asymptomatic-colonization-to-invasive-disease
#13
Ryan M Reddinger, Nicole R Luke-Marshall, Anders P Hakansson, Anthony A Campagnari
UNLABELLED: Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease. S. aureus is a major source of severe secondary bacterial pneumonia after influenza A virus infection, which causes widespread morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is well established, the mechanisms behind the transition from asymptomatic colonization to invasive staphylococcal disease following viral infection remains unknown...
2016: MBio
https://www.readbyqxmd.com/read/27505057/an-epithelial-integrin-regulates-the-amplitude-of-protective-lung-interferon-responses-against-multiple-respiratory-pathogens
#14
Victoria A Meliopoulos, Lee-Ann Van de Velde, Nicholas C Van de Velde, Erik A Karlsson, Geoff Neale, Peter Vogel, Cliff Guy, Shalini Sharma, Susu Duan, Sherri L Surman, Bart G Jones, Michael D L Johnson, Catharine Bosio, Lisa Jolly, R Gisli Jenkins, Julia L Hurwitz, Jason W Rosch, Dean Sheppard, Paul G Thomas, Peter J Murray, Stacey Schultz-Cherry
The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27486731/human-influenza-virus-infections
#15
Christin Peteranderl, Susanne Herold, Carole Schmoldt
Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact...
August 2016: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27476045/14-deoxy-11-12-didehydroandrographolide-attenuates-excessive-inflammatory-responses-and-protects-mice-lethally-challenged-with-highly-pathogenic-a-h5n1-influenza-viruses
#16
Wentao Cai, Sunrui Chen, Yongtao Li, Anding Zhang, Hongbo Zhou, Huanchun Chen, Meilin Jin
Traditional Chinese medicine (TCM) has been an excellent treasury for centuries' accumulation of clinical experiences, which deserves to be tapped for potential drugs and improved using modern scientific methods. 14-Deoxy-11,12-didehydroandrographolide (DAP), a major component of an important TCM named Andrographis paniculata, with non-toxic concentration of 1000 mg/kg/day, effectively reduced the mortality and weight loss of mice lethally challenged with A/chicken/Hubei/327/2004 (H5N1) or A/PR/8/34 (H1N1) influenza A viruses (IAV) when initiated at 4 h before infection, or A/duck/Hubei/XN/2007 (H5N1) when initiated at 4 h or 48 h before infection, or 4 h post-infection (pi)...
September 2016: Antiviral Research
https://www.readbyqxmd.com/read/27466426/hiv-dna-is-frequently-present-within-pathologic-tissues-evaluated-at-autopsy-from-combined-antiretroviral-therapy-treated-patients-with-undetectable-viral-loads
#17
Susanna L Lamers, Rebecca Rose, Ekaterina Maidji, Melissa Agsalda-Garcia, David J Nolan, Gary B Fogel, Marco Salemi, Debra L Garcia, Paige Bracci, William Yong, Deborah Commins, Jonathan Said, Negar Khanlou, Charles H Hinkin, Miguel Valdes Sueiras, Glenn Mathisen, Suzanne Donovan, Bruce Shiramizu, Cheryl A Stoddart, Michael S McGrath, Elyse J Singer
UNLABELLED: HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort...
October 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27436444/mycoplasma-hyorhinis-is-a-potential-pathogen-of-porcine-respiratory-disease-complex-that-aggravates-pneumonia-caused-by-porcine-reproductive-and-respiratory-syndrome-virus
#18
Jung-Ah Lee, Yu-Ri Oh, Min-A Hwang, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Sang-Won Lee
The porcine respiratory disease complex (PRDC) caused by numerous bacterial and viral agents has a great impact on pig industry worldwide. Although Mycoplasma hyorhinis (Mhr) has been frequently isolated from lung lesions from pigs with PRDC, the pathological importance of Mhr may have been underestimated. In this study, 383 serum samples obtained from seven herds with a history of PRDC were tested for specific antibodies to Mhr, Mycoplasma hyopneumoniae (Mhp), and porcine reproductive and respiratory syndrome virus (PRRSV)...
September 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27357918/a-clinically-authentic-mouse-model-of-enterovirus-71-ev-a71-induced-neurogenic-pulmonary-oedema
#19
Carla Bianca Luena Victorio, Yishi Xu, Qimei Ng, Beng Hooi Chua, Sylvie Alonso, Vincent T K Chow, Kaw Bing Chua
Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)-the main cause of EV-A71 infection-related mortality-is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27341844/combination-activity-of-neuraminidase-inhibitor-oseltamivir-and-%C3%AE-tocopherol-in-influenza-virus-a-h3n2-infection-in-mice
#20
Angel S Galabov, Milka Mileva, Lora Simeonova, Galina Gegova
BACKGROUND: Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis-viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. METHODS: After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2...
August 2015: Antiviral Chemistry & Chemotherapy
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