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replication but also to control the inflammatory response . The activity of many of the proteins participating in the signaling cascade is influenced by post-translational modifications, such as covalent linkage of ubiquitine or other tags (ISG15) . Our results show that the expression of certain genes involved in the innate immune response, as well as RSV replication are regulated by these processes of ubiquitination and ISGylation .
Most relevant scientific articles
• díez-doMINGo J., perez-Yarza e.G., MeLero J.a., SaNchez-LuNa M., aGuILar M.d., BLaSco a.J. et al . Social, economic, and health impact of the respiratory syncytial virus: A systematic search . BMC Infectious Diseases . 2014;:544 .
• SWaNSoN k.a., BaLaBaNIS k., xIe Y., aGGarWaL Y., paLoMo c., MaS V . et al . A monomeric uncleaved respiratory syncytial virus F antigen retains prefusion-specific neutralizing epitopes . Journal of Virology . 2014;88(20):11802-11810 .
• García-BarreNo B., deLGado t., BeNIto S., caSaS I., pozo F., MeLero J.a. . Exploring the antigenic relatedness of influenza virus haemagglutinins with strain-specific polyclonal antibodies . Journal of General Virology . 2014;95:2140-2145 .
• paLoMo c., MaS V., Vazquez M., caNo o., Luque d., terroN M.c. et al . Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation . Virology . 2014;460-461(1):119-127 .
• García-BarreNo B., deLGado t., BeNIto S., caSaS I., pozo F., cueVaS M.t. et al . Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin . Journal of General Virology . 2014;95(PART 5):1033-1042 .
Highlights
Institution: Instituto de Salud Carlos III Contact: C . Nacional de Microbiologia . Campus Majadahonda . Ctra . Majadahonda -Pozuelo km 2 .200 . 28220 Majadahonda, Madrid · Phone: (+34) 91 822 39 08 · E .mail: jmelero@isciii .es
ACTIVE RESEARCH PROJECTS IN 2014
• Title: Membrane fusión mediated by the pneumovirus F protein and conformation specific antibodies: two new paradigms for clinical intervention against these viruses . Funding agency: Plan Nacional de I+D+i . Dura- tion: January 2013-December 2015 . Budget: 339 .300 € .
• Title: Regulation by deubiquitinases of the inflammatory response induced by human respiratory syncytial virus . Funding agency: FIS . Duration: January 2012-December 2015 . Budget: 86 .212,50 .
MOST RELEVANT RESEARCH RESULTS ACHIEVED IN 2014
• Design and development of new methods for the antigenic characterization of the influenza virus haema- gglutinin (HA) with strain specific polyclonal antibodies and mapping of relevant antigenic sites .
• Design and development of new methods for the isolation of postfusion specific monoclonal antibodies di- rected against the Pneumovirinae fusion protein .
• Identification and characterization of a new monomeric form of the Pneumovirinae fusion protein.
• Demonstration of the ISG15 antiviral effect at early stages of human respiratory syncytial virus (HRSV) repli- cation through covalent binding to target proteins (ISGylation) . Furthermore, ISG15 accumulation and corre- lation with virus load in nasopharyngeal washes from infected children, suggesting that ISG15 may also have an anti-HRSV effect in vivo .
• Demonstration of HRSV induced DNA degradation and cell senescence in vitro (A549 cells) and in vivo, respi- ratory epithelium of mice .
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