PB1-F2; Bacterial super infection; Influenza A virus; Microbiome
Yángüez Emilio, Hunziker Annika, Dobay Maria Pamela, Yildiz Soner, Schading Simon, Elshina Elizaveta, Karakus Umut, Gehrig Peter, Grossmann Jonas, Dijkman Ronald, Schmolke Mirco, Stertz Silke (2018), Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target, in Nature Communications
, 9(1), 3679-3679.
Yildiz Soner, Mazel-Sanchez Béryl, Kandasamy Matheswaran, Manicassamy Balaji, Schmolke Mirco (2018), Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis, in Microbiome
, 6(1), 9-9.
Anchisi Stéphanie, Gonçalves Ana Rita, Mazel-Sanchez Béryl, Cordey Samuel, Schmolke Mirco (2018), Influenza VirusMethods and Protocols
, Springer New York, New York, NY.
Mazel-Sanchez B., Boal-Carvalho I., Silva F., Dijkman R., Schmolke M. (2018), H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells, in Journal of Virology
, 92(11), e00425-18-e00425-18.
Vono Maria, Eberhardt Christiane Sigrid, Mohr Elodie, Auderset Floriane, Christensen Dennis, Schmolke Mirco, Coler Rhea, Meinke Andreas, Andersen Peter, Lambert Paul-Henri, Mastelic-Gavillet Beatris, Siegrist Claire-Anne (2018), Overcoming the Neonatal Limitations of Inducing Germinal Centers through Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or Curdlan, in Frontiers in Immunology
, 9, 381.
Kandasamy Matheswaran, Suryawanshi Amol, Tundup Smanla, Perez Jasmine T., Schmolke Mirco, Manicassamy Santhakumar, Manicassamy Balaji (2016), RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection, in PLOS Pathogens
, 12(7), e1005754-e1005754.
Influenza A virus (IAV) is a major human respiratory pathogen causing outbreaks with annual global attack rates of 5-10% for adults and 20-30% for children, resulting in estimated 5 million severe cases annually, 250000-500000 with fatal outcome (estimated numbers by World Health Organization (WHO, http://www.who.int/mediacentre/factsheets/fs211/en/ and http://www.who.int/biologicals/ vaccines/influenza/en/ ). High-risk groups include infants, elderly and immune compromised patients. One of the major complications in IAV infections is bacterial super infection. During the 1918 Spanish influenza outbreak the majority of infected patients died of bacterial super infections. Even less devastating seasonal influenza infections result in bacterial super infections in up to 15% of the cases. The mechanisms by which IAV supports this subsequent super infection with pathogenic respiratory bacteria like Streptococcus pneumoniae, Staphylococcus aureus or Haemophilus influenzae are matter of ongoing research. Viral pathogenicity factors like the accessory protein PB1-F2 have been shown to enhance bacterial super infections in animal models, although the mechanisms of this enhancement are far from being understood. Recent reports indicate that IAV infections not only increase susceptibility of super infections with pathogenic bacteria but significantly impact the composition of host lung microbiota. At the same time host microbiota are required for efficient priming of immune responses against IAV infections. To better understand the triangular relationship of host, microbiota and invading virus we propose experiments that will address the impact of host innate immunity on microbiome composition during IAV infection. We will test if and how pathogenicity factors like PB1-F2 affect the composition of the host microbiome during IAV infection. Furthermore, we will determine if these changes in microbiome influence the host susceptibility towards bacterial super infections, which in the long run might help to discriminate between useful, expendable or harmful commensal bacteria. Finally, we are aiming to understand how IAV PB1-F2 increases susceptibility to bacterial super infection on a molecular level, by identification of host factors that interact with PB1-F2. The suggested projects could reveal new diagnostic markers that can be used to determine when use of antibiotics is likely to prevent super infections after IAV infection and identify host factors that might contribute to bacterial super infection.