Yellow fever virus (YFV) is the etiologic agent of yellow fever. There are no antivirals available to treat yellow fever, and attempts to develop YFV-specific antivirals or to develop alternative vaccines have been hampered by the lack of an immunocompetent mouse model of yellow fever. It has been reported that both the wild-type (Asibi) strain and the 17D strain of yellow fever infect mice with defects in type I IFN (IFN-I) signaling. This suggests that the IFN-I response serves as the major barrier to mouse infection. We have recently shown that YFV antagonizes IFN-I signaling in human and non-human primate cells and that the NS5 proteins of both YFV-Asibi and YFV-17D bind to and sequester human STAT2 after interferon signaling. My research project’s aim is to identify the host restriction factors responsible for the inability of the YF-NS5 protein to bind to murine STAT2 and inhibit murine IFN-I signaling. This will be potentially useful for the development of a Yellow Fever mouse model.
Giuseppe Pisanelli, Maudry Laurent-Rolle, Balaji Manicassamy, Alan Belicha-Villanueva, Juliet Morrison, Bernardo Lozano-Dubernard, Felipa Castro-Peralta, Giuseppe Iovane, and Adolfo García-Sastre. La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation. Virus Research. 2016 Feb 2;213:11-22. doi: 10.1016/j.virusres.2015.10.027.
Maudry Laurent-Rolle, Juliet Morrison, Ricardo Rajsbaum, Jesica M. Levingston Macleod, Giuseppe Pisanelli, Alissa Pham, Juan Ayllon, Lisa Miorin, Carles Martínez-Romero, Benjamin R Tenoever, and Adolfo García-Sastre. The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by Type I interferon. Cell Host and Microbes. 2014 Sep 10;16(3):314-27. doi: 10.1016/j.chom.2014.07.015.
Ricardo Rajsbaum, Gijs A. Versteeg, Sonja Schmid, Ana M. Maestre, Alan Belicha-Villanueva, Carles Martínez-Romero, Jenish R. Patel, Juliet Morrison, Giuseppe Pisanelli, Lisa Miorin, Maudry Laurent-Rolle, Hong M. Moulton, David A. Stein, Ana Fernandez-Sesma, Benjamin R. Tenoever, and Adolfo García-Sastre. Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKKε Kinase-Mediated Antiviral Response. Immunity. 2014 Jun 19;40(6):880-95. doi: 10.1016/j.immuni.2014.04.018. Epub 2014 May 29. PMID: 24882218.
Juliet Morrison, Maudry Laurent-Rolle, Ana Maestre, Giuseppe Pisanelli, Lubbertus C.F. Mulder, Viviana Simon, Ana Fernandez-Sesma, Adolfo García-Sastre. Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I IFN signaling. PLOS Pathogens. 2013 Mar;9(3):e1003265. doi: 10.1371/journal.ppat.1003265. Epub 2013 Mar 28.
Balaji Manicassamy, Santhakumar Manicassamy, Alan Belicha-Villanueva, Giuseppe Pisanelli, Bali Pulendran And Adolfo García-Sastre. Analysis of in vivo dynamics of influenza virus infection using a GFP reporter virus. Proceedings of National Academy of Sciences of the United States of America. 2010 Jun 22;107(25):11531-6. Epub 2010 Jun 7.