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| emerging viruses | |
Flaviviruses: Dengue (DEN) and West Nile Virus (WNV)Flaviviruses are emerging vector-borne pathogens capable of causing severe human diseases including yellow fever, dengue fever, and encephalitis. Dengue fever virus (DEN) has re-emerged as a major pathogen in tropical Latin America, and West Nile virus (WNV) has emerged throughout the United States. Current research on flaviviruses focuses on the identification and characterization of viral encoded interferon (IFN) antagonists. We have developed reporter systems to identify flavivirus proteins that block IFN signaling or enhance viral replication in the presence of IFN. With these molecular studies, we hope to uncover mechanisms governing pathogenesis of dengue and West Nile, and are collaborating with other members of the Northeast Biodefense Center in these efforts. Crimean-Congo Hemorrhagic Fever Virus (CCHFV) A human nairovirus, CCHFV is a negative-sense segmented member of the Bunyaviridae. Our research aims at understanding components of the replication machinery and the role of the L protein's ovarian-tumor (OTU) domain in evading antiviral response. A prominent IFN-induced antiviral protein, ISG15, is conjugated onto cellular and viral targets in a manner similar to ubiquitin. The CCHFV L protein OTU domain is capable of acting as an ISG15 antagonist. By disrupting ISG15 activity, the CCHFV L protein disrupts the antiviral state induced by type I IFNs and potentially facilitates virus replication and survival. We are also characterizing cis- and trans- signals involved in replication of CCHFV RNA. With this we hope to further understand the molecular basis of pathogenesis of CCHFV. A. BERTOLOTTI-CIARLET, J. SMITH, K. STRECKER, J. PARAGAS, L.A. ALTAMURA, J.M. McFALLS, N. FRIAS-STÄHELI, A. GARCÍA-SASTRE, C.S. SCHMALJOHN & R.W. DOMS: Cellular localization and antigenic characterization of Crimean-Congo hemorrhagic fever virus glycoproteins. Journal of Virology, 79, 6152-6161 (2005). J.L. MUÑOZ-JORDÁN, M. LAURENT-ROLLE, J. ASHOUR, L MARTÍNEZ-SOBRIDO, M. ASHOK, W.I. LIPKIN & A. GARCÍA-SASTRE: Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. Journal of Virology, 79, 8004-8013 (2005). J.L. MUÑOZ-JORDÁN, G.G. SÁNCHEZ-BURGOS, M. LAURENT-ROLLE & A. GARCÍA-SASTRE: Inhibition of interferon signaling by dengue virus. Proceedings of the National Academy of Sciences (U.S.A.), 100, 14333-14338 (2003). |
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| Copyright © 2007, Mount Sinai School of Medicine |
