Evasion of the Interferon-Mediated Antiviral Response by Filoviruses.docVIP

Viruses 2010, 2, 262-282; doi:10.3390/v2010262 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Evasion of the Interferon-Mediated Antiviral Response by Filoviruses Washington B. Cárdenas Laboratorio de Biomedicina, FIMCM, Escuela Superior Politécnica del Litoral (ESPOL), Campus Gustavo Galindo, Km 30.5 via Perimetral, Apartado 09-01-5863, Guayaquil, Ecuador; E-Mail: wbcarden@.ec; Tel.: +5934 226 9589; Fax: +5934 285 0663 Received: 3 September 2009; in revised form: 11 January 2010 / Accepted: 19 January 2010 / Published: 21 January 2010 Abstract: The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs) that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN) antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV), the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production o