scholarly journals Novel endosomal NOX2 oxidase inhibitor ameliorates pandemic influenza A virus‐induced lung inflammation in mice

Respirology ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1011-1017 ◽  
Author(s):  
Eunice E. To ◽  
Raymond Luong ◽  
Jiayin Diao ◽  
John J. O’ Leary ◽  
Doug A. Brooks ◽  
...  
2019 ◽  
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  

AbstractThe virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔvisR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.Author summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.


2009 ◽  
Vol 82 (2) ◽  
pp. A70-A71
Author(s):  
François Jean ◽  
Vesna Posarac ◽  
Peter Cheung ◽  
Martine Boutin ◽  
Heather Braybrook ◽  
...  

Critical Care ◽  
2014 ◽  
Vol 18 (3) ◽  
pp. R127 ◽  
Author(s):  
Estefanía Herrera-Ramos ◽  
Marta López-Rodríguez ◽  
José Ruíz-Hernández ◽  
Juan Horcajada ◽  
Luis Borderías ◽  
...  

2010 ◽  
Vol 164 (1-2) ◽  
pp. 83-87 ◽  
Author(s):  
Alessio Lorusso ◽  
Kay S. Faaberg ◽  
Mary Lea Killian ◽  
Leo Koster ◽  
Amy L. Vincent

2012 ◽  
Vol 93 (8) ◽  
pp. 1658-1663 ◽  
Author(s):  
Elke Starick ◽  
Elke Lange ◽  
Christian Grund ◽  
Elisabeth grosse Beilage ◽  
Stefanie Döhring ◽  
...  

The incursion of the human pandemic influenza A virus H1N1 (2009) (H1N1 pdm) into pig populations and its ongoing co-circulation with endemic swine influenza viruses (SIVs) has yielded distinct human–porcine reassortant virus lineages. The haemagglutinin (HA) gene of H1N1 pdm was detected in 41 influenza virus-positive samples from seven swine herds in north-west Germany in 2011. Eight of these samples yielded virus that carried SIV-derived neuraminidase N2 of three different porcine lineages in an H1N1 pdm backbone. The HA sequences of these viruses clustered in two distinct groups and were distinguishable from human and other porcine H1 pdm by a unique set of eight non-synonymous mutations. In contrast to the human population, where H1N1 pdm replaced seasonal H1N1, this virus seems to co-circulate and interact more intensely with endemic SIV lineages, giving rise to reassortants with as-yet-unknown biological properties and undetermined risks for public health.


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