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Pathogenesis of viral infection of the lungs

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https://www.readbyqxmd.com/read/29740449/protective-role-of-nuclear-factor-erythroid-2-related-factor-2-against-respiratory-syncytial-virus-and-human-metapneumovirus-infections
#1
Teodora Ivanciuc, Elena Sbrana, Antonella Casola, Roberto P Garofalo
The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant-antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29706970/h7n9-avian-influenza-virus-is-efficiently-transmissible-and-induces-an-antibody-response-in-chickens
#2
Peirong Jiao, Yafen Song, Jianni Huang, Chengwei Xiang, Jin Cui, Siyu Wu, Nannan Qu, Nianchen Wang, Guowen Ouyang, Ming Liao
H7N9 viruses pose a threat to human health and they are no less harmful to the poultry industry than the H5N1 avian influenza viruses. However, the pathogenesis, transmissibility, and the host immune response of the H7N9 virus in chickens and mice remain unclear. In this study, we found that H7N9 viruses replicated in multiple organs of the chicken and viral shedding persisted up to 30 days postinoculation (DPI). The viruses were efficiently transmitted between chickens through direct contact. Notably, chickens infected with H7N9 had high antibody levels throughout the entire observation period and their antibody response lasted for 30 DPI...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29691378/blockade-of-the-c5a-c5ar-axis-alleviates-lung-damage-in-hdpp4-transgenic-mice-infected-with-mers-cov
#3
Yuting Jiang, Guangyu Zhao, Nianping Song, Pei Li, Yuehong Chen, Yan Guo, Junfeng Li, Lanying Du, Shibo Jiang, Renfeng Guo, Shihui Sun, Yusen Zhou
The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage...
April 24, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29656244/human-organoid-cultures-transformative-new-tools-for-human-virus-studies
#4
REVIEW
Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K Estes
Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids)...
April 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29621732/c5a-receptor1-inhibition-alleviates-influenza-virus-induced-acute-lung-injury
#5
Nianping Song, Pei Li, Yuting Jiang, Hong Sun, Jing Cui, Guangyu Zhao, Dan Li, Yan Guo, Yuehong Chen, Jimin Gao, Shihui Sun, Yusen Zhou
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection...
April 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29597193/zika-virus-pathogenesis-in-infant-mice-after-natural-transmission-by-the-bite-of-infected-mosquitoes
#6
Pragya D Yadav, Vimal Kumar, Sandeep Kumar, Chandrashekhar S Mote, Triparna D Majumdar, Mangesh Gokhale, Pravin Kore, Devendra T Mourya
OBJECTIVES: The objective of this study was to understand natural disease progression in infant CD1 mice after the bite of Aedes aegypti mosquitoes infected by the Zika virus (ZIKV, MR-766 strain). METHODS: A. aegypti mosquitoes were experimentally infected with ZIKV MR-766 strain via the oral feeding route. Infected mosquitoes were allowed to feed on infant CD1 mice. Sick mice were euthanized, and their organs were collected and subjected to real-time RT-PCR, histo-pathology, and immunohistochemistry...
March 29, 2018: Intervirology
https://www.readbyqxmd.com/read/29594984/in-vivo-characterization-of-macrophage-tropic-simian-immunodeficiency-virus-molecular-clones-in-rhesus-macaques
#7
Sanjeev Gumber, Praveen Kumar Amancha, Po-Jen Yen, Francois Villinger, Dana Gabuzda, Siddappa N Byrareddy
Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads...
March 28, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29558354/-the-changing-face-of-medium-sized-vasculitis
#8
Jolanta Parada-Turska, Monika Turska
Polyarteritis nodosa is a systemic necrotizing vasculitis which predominantly affects medium-sized arteries. It is a rare disease nowadays. Both the nomenclature and the classification of polyarteritis nodosa was amended several times in the past. Currently, there is a distinction between the primary form described as classical polyarteritis nodosa and other forms that are associated with their probable cause e.g. with viral hepatitis B, C or HIV infection. Moreover, polyarteritis-like necrotizing vasculitis can appear in the course of genetic diseases caused by mutations in single genes...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29514908/porcine-mkrn1-modulates-the-replication-and-pathogenesis-of-porcine-circovirus-type-2-by-inducing-capsid-protein-ubiquitination-and-degradation
#9
Tongtong Wang, Qian Du, Xingchen Wu, Yingying Niu, Lijuan Guan, Zhenyu Wang, Xiaomin Zhao, Shan-Lu Liu, Dewen Tong, Yong Huang
Porcine circovirus type 2 (PCV2) capsid protein (Cap) is a unique structure protein that plays pivotal roles in the process of viral replication and pathogenesis. Herein, we characterized a putative porcine Makorin RING finger protein 1 (pMKRN1) variant, an N-terminal-truncated variant of putative full-size porcine MKRN1 which has a unique expression pattern resulting from the porcine mkrn1 gene and which interacts with PCV2 Cap. A domain mapping assay showed that the C terminus of pMKRN1 and fragments (amino acids 108 to 198) of Cap are required for this interaction...
June 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29447290/a-neonatal-murine-model-for-evaluation-of-enterovirus-e-hy12-virus-infection-and-pathogenicity
#10
Xiaochun Gai, Qun Zhang, Haibing Lu, Zhanqing Yang, Lisai Zhu, Xin Li, Xinping Wang
BACKGROUNDS: HY12 viruses are enteroviruses recently isolated from cattle characterized by severe respiratory and digestive disease with high morbidity and mortality in China. While the viruses exhibit unique biological and molecular characters distinct from known enterovirus E, the pathogenicity and viral pathogenesis remains largely unknown. METHODS: Neonatal mice of Balb/C, ICR, and Kunming strain are infected with HY12 to determine the susceptible mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29445124/efficacy-of-mucosal-polyanhydride-nanovaccine-against-respiratory-syncytial-virus-infection-in-the-neonatal-calf
#11
Jodi L McGill, Sean M Kelly, Pankaj Kumar, Savannah Speckhart, Shannon L Haughney, Jamie Henningson, Balaji Narasimhan, Randy E Sacco
Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to RSV infection in humans, including similar age dependency and disease pathogenesis. Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have shown promise as adjuvants and vaccine delivery vehicles due to their ability to promote enhanced immunogenicity through the route of administration, provide sustained antigen exposure, and induce both antibody- and cell-mediated immunity...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29432231/noncommunicable-diseases-in-adolescents-with-perinatally-acquired-hiv-1-infection-in-high-income-and-low-income-settings
#12
Steve Innes, Kunjal Patel
PURPOSE OF REVIEW: Perinatally HIV-infected adolescents may be at increased risk of noninfectious comorbidities later in life. This review summarizes recent advances in the understanding of noncommunicable diseases (NCD) among HIV-infected adolescents in high-income and lower middle-income countries, and identifies key questions that remain unanswered. We review atherosclerotic vascular disease (AVD), chronic bone disease (CBD), chronic kidney disease (CKD), and chronic lung disease (CLD)...
May 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29390024/viral-fgarat-orf75a-promotes-early-events-in-lytic-infection-and-gammaherpesvirus-pathogenesis-in-mice
#13
Nick D Van Skike, Nana K Minkah, Chad H Hogan, Gary Wu, Peter T Benziger, Darby G Oldenburg, Mehmet Kara, Deborah M Kim-Holzapfel, Douglas W White, Scott A Tibbetts, Jarrod B French, Laurie T Krug
Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen...
February 2018: PLoS Pathogens
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
#14
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 α4 β7 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 α4 β7 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 α4 β7 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
#15
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
#16
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
#17
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...
February 1, 2018: 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
#18
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...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29237287/early-sites-of-virus-replication-after-oral-siv-mac251-infection-of-infant-macaques-implications-for-pathogenesis
#19
Angela M Amedee, Bonnie Phillips, Kara Jensen, Spencer Robichaux, Nedra Lacour, Mark Burke, Michael Piatak, Jeffrey D 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 through 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 simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIVmac251 exposure. SIV DNA was detected as early as 48 h, whereas SIV RNA was typically detected at later time points (72-96 h)...
January 17, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29175108/nonstructural-protein-2a-modulates-replication-and-virulence-of-enterovirus-71
#20
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...
January 15, 2018: Virus Research
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