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Pneumonia virus of mice

Elena S Don, Alexandra G Emelyanova, Natalia N Yakovleva, Nataliia V Petrova, Marina V Nikiforova, Evgeniy A Gorbunov, Sergey A Tarasov, Sergey G Morozov, Oleg I Epstein
The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0...
October 21, 2016: Journal of Medical Virology
Wenfei Zhu, Hong Zhang, Xingyu Xiang, Lili Zhong, Lei Yang, Junfeng Guo, Yiran Xie, Fangcai Li, Zhihong Deng, Hong Feng, Yiwei Huang, Shixiong Hu, Xin Xu, Xiaohui Zou, Xiaodan Li, Tian Bai, Yongkun Chen, Zi Li, Junhua Li, Yuelong Shu
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus...
November 2016: Emerging Infectious Diseases
Paul M Arnaboldi, Mariya Sambir, Christina D'Arco, Lauren A Peters, Jos F M L Seegers, Lloyd Mayer, Alison A McCormick, Raymond J Dattwyler
Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y...
October 13, 2016: Vaccine
Dalit Talmi-Frank, Zeev Altboum, Inna Solomonov, Yael Udi, Diego Adhemar Jaitin, Mordehay Klepfish, Eyal David, Alina Zhuravlev, Hadas Keren-Shaul, Deborah R Winter, Irit Gat-Viks, Michal Mandelboim, Tamar Ziv, Ido Amit, Irit Sagi
Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage...
October 12, 2016: Cell Host & Microbe
Xiang Xu, John R Greenland, Jeffrey E Gotts, Michael A Matthay, George H Caughey
Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl-/- mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl+/+ mice...
2016: PloS One
Karl O A Yu, Adrienne G Randolph, Anna A Agan, Wai-Ki Yip, Edward Truemper, Scott Weiss, Kate Ackerman, Adam Schwarz, John Guiliani, Mark W Hall, Juliane Bubeck Wardenburg
BACKGROUND:  Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral co-infection is unclear. METHODS:  We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza infection...
September 20, 2016: Journal of Infectious Diseases
Vicente Más, Laura Rodriguez, Eduardo Olmedillas, Olga Cano, Concepción Palomo, María C Terrón, Daniel Luque, José A Melero, Jason S McLellan
Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 Å by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV)...
September 2016: PLoS Pathogens
Niels A W Lemmermann, Matthias J Reddehase
With the cover headline 'T cells on the attack,' the journal Science celebrated individualized cancer immunotherapy by adoptive transfer of T cells as the 'Breakthrough of the Year' 2013 (J. Couzin-Frankel in Science 342:1432-1433, 2013). It is less well recognized and appreciated that individualized T cell immunotherapy of cytomegalovirus (CMV) infection is approaching clinical application for preventing CMV organ manifestations, interstitial CMV pneumonia in particular. This coincident medical development is particularly interesting as reactivated CMV infection is a major viral complication in the state of transient immunodeficiency after the therapy of hematopoietic malignancies by hematopoietic cell transplantation (HCT)...
August 18, 2016: Medical Microbiology and Immunology
Anandi Narayana Moorthy, Kong Bing Tan, Shi Wang, Teluguakula Narasaraju, Vincent T Chow
Obesity is an independent risk factor for severe outcome of influenza infection. Higher dietary fat consumption has been linked to greater morbidity and severe influenza in mouse models. However, the extent of generation of neutrophil extracellular traps (NETs or NETosis) in obese individuals during influenza pneumonia is hitherto unknown. This study investigated pulmonary NETs generation in BALB/c mice fed with high-fat diet (HFD) and low-fat diet (LFD), during the course of influenza pneumonia. Clinical disease progression, histopathology, lung reactive oxygen species, and myeloperoxidase activity were also compared...
2016: Frontiers in Immunology
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
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
Tatsuhiko Harada, Yuji Ishimatsu, Atsuko Hara, Towako Morita, Shota Nakashima, Tomoyuki Kakugawa, Noriho Sakamoto, Kosuke Kosai, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae, Shigeru Kohno
Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Meng Yu, Qingnan Wang, Wenbao Qi, Kaizhao Zhang, Jianxin Liu, Pan Tao, Shikun Ge, Ming Liao, Zhangyong Ning
H7N9 influenza A virus (IAV)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. Host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced "cytokine storm" also leads to pathological lesions. However, what inflammation-related response of the host for H7N9 influenza A virus infection to survival from injures of exuberant cytokine release is still obscure. In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1β, TNF-α, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 residue 627 difference were investigated, as well as the histopathological injury of the lung...
October 2016: Medical Microbiology and Immunology
Yuexia Ma, Wei Zhang, Zhongpeng Zhao, Min Li, Jian Liu, Yuguang Wang
OBJECTIVE: To investigate the effects of ribavirin administration combined with Reduning in a mouse model of influenza A (H1N1)-induced severe pneumonia. METHODS: Influenza A/Beijing/501/2009 (H1N1)-infected C57BL/6 mice were randomly divided into four experimental groups treated with either a mock injection of phosphate-buffered saline (PBS), ribavirin (66.6 mg/kg daily) or Reduning (86.6 mg/ kg daily), or a combination of both, for 7 days. Mice were monitored for clinical signs and survival, and body weight was measured daily for 14 days...
April 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
Pratima Shrivastava, Indranil Sarkar, Ethel Atanley, Susantha Gomis, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and pneumonia in infants and pneumonia virus of mice (PVM) causes similar disease. BALB/c mice are highly susceptible, while C57BL/6 mice are more resistant to PVM. IL-12 was significantly more up-regulated in response to PVM infection in BALB/c than in C57BL/6 mice. IL-12p40-deficient neonatal and adult BALB/c mice showed significantly less weight loss than wild-type mice after PVM challenge. The percentage of regulatory T cells, as well as IFN-β and IL-18 expression, was higher in the lungs of both neonatal and adult IL-12p40-/- mice...
October 2016: Virology
Swapnil S Bawage, Pooja M Tiwari, Ankur Singh, Saurabh Dixit, Shreekumar R Pillai, Vida A Dennis, Shree R Singh
Respiratory syncytial virus (RSV) causes severe pneumonia and bronchiolitis in infants, children and older adults. The use of metallic nanoparticles as potential therapeutics is being explored against respiratory viruses like Influenza, Parainfluenza and Adenovirus. In this study, we showed that gold nanorods (GNRs) inhibit RSV in HEp-2 cells and BALB/c mice by 82% and 56%, respectively. The RSV inhibition correlated with marked upregulated antiviral genes due to GNR mediated TLR, NOD-like receptor and RIG-I-like receptor signaling pathways...
July 2, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Kazuma Yagi, Makoto Ishii, Ho Namkoong, Hideki Fujii, Takahiro Asami, Shoji Suzuki, Takanori Asakura, Kosuke Mizoguchi, Tetsuro Kamo, Sadatomo Tasaka, Satoshi Iwata, Steven L Kunkel, Naoki Hasegawa, Tomoko Betsuyaku
OBJECTIVES: Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. Epigenetic gene regulation appears to play key roles in innate and adaptive immunity. We hypothesized that histone acetylation, a major epigenetic mechanism associated with transcriptionally active chromatin, might contribute to the poor outcome of postinfluenza pneumonia. DESIGN: Prospective experimental study. SETTING: University research laboratory...
October 2016: Critical Care Medicine
Yun Li, Yanni Lai, Yao Wang, Ni Liu, Fengxue Zhang, Peiping Xu
1,8-Cineol is a major monoterpene principally from eucalyptus essential oils and has been shown to exert anti-inflammatory, antiviral, and inhibitory of nuclear factor (NF)-kB effect. In the present study, we evaluated the effect of 1,8-cineol on mice infected with influenza A virus. We found that 1,8-cineol protects against influenza viral infection in mice. Moreover, 1,8-cineol efficiently decreased the level of IL-4, IL-5, IL-10, and MCP-1 in nasal lavage fluids and the level of IL-1β, IL-6, TNF-α, and IFN-γ in lung tissues of mice infected with influenza virus...
August 2016: Inflammation
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
Teodora Ivanciuc, Elena Sbrana, Maria Ansar, Nikolay Bazhanov, Csaba Szabo, Antonella Casola, Roberto P Garofalo
RATIONALE: Hydrogen sulfide (H2S) is an endogenous gaseous transmitter whose role in the pathophysiology of several lung diseases has been increasingly appreciated. Our recent studies in vitro have shown for the first time that H2S has an important antiviral and anti-inflammatory activity in respiratory syncytial virus (RSV) infection, the leading cause of bronchiolitis and viral pneumonia in children. OBJECTIVES: To evaluate the therapeutic potential of GYY4137, a novel slow-releasing H2S donor, for prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mouse model of RSV infection...
June 17, 2016: American Journal of Respiratory Cell and Molecular Biology
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