Raquel
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- The woodchuck interferon-alpha system: Cloning, family description, and biologic activity(Wiley-Blackwell, 2002) Riezu-Boj, J.I. (José Ignacio); Berraondo, P. (Pedro); González-Aseguinolaza, G. (Gloria); Vales, A. (África); Larrea, E. (Esther); Raquel; Prieto, J. (Jesús); Blanco-Urgoiti, B. (Begoña); Ruiz, J. (Juan)Interferon-alpha (IFN-alpha) is a key element in the defense against viral infection because, in addition to a direct antiviral effect, it exhibits potent immunostimulatory activity. To investigate the function of this cytokine in the woodchuck model of chronic hepatitis B, the woodchuck IFN-alpha gene (IFNA) family was cloned and examined. The data indicate that this is a multigenic family from which 12 IFNA functional sequences and four pseudogene sequences were isolated. The overall identity of the amino acid sequence among the members of the woodchuck IFN-alpha family is 85%, and the identity with the IFN-alpha family from other species such as mice and humans is 50%. The analysis of hepatic expression of IFNA genes showed that wIFNA5a was the subtype transcribed preferentially in the woodchuck liver. The wIFNA genes transcribed in the liver were tested in an eukaryotic expression system and were found to enhance 2-5-oligoadenylate synthetase (2-5-OAS) mRNA levels and to posses a potent antiviral activity. Cloning of woodchuck IFNA genes will allow testing diverse forms of IFN-alpha delivery as well as different combination therapies in woodchuck hepatitis virus infection, thus providing useful information for the design of new strategies for the treatment of patients with chronic hepatitis B.
- Protection against woodchuck hepatitis virus (WHV) infection by gene gun coimmunization with WHV core and interleukin-12(American Society for Microbiology, 2001) Berraondo, P. (Pedro); Vales, A. (África); Borras-Cuesta, F. (Francisco); Sanchez-de-la-Rosa, R. (R.); Raquel; Hervas-Stubbs, S. (Sandra); Prieto, J. (Jesús); Blanco-Urgoiti, B. (Begoña); Ruiz, J. (Juan); Lasarte, J.J. (Juan José)Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against infection. Here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of WHcAg-specific T cells but that these cells do not produce significant levels of gamma interferon (IFN-gamma) upon antigen stimulation. In addition, animals vaccinated with pCw alone were not protected against WHV inoculation. In order to induce a Th1 cytokine response, another group of woodchucks was immunized with pCw together with another plasmid coding for woodchuck interleukin-12 (IL-12). These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma production and were protected against challenge with WHV, showing no viremia or low-level transient viremia after WHV inoculation. In conclusion, gene gun immunization with WHV core generates a non-Th1 type of response which does not protect against experimental infection. However, steering the immune response to a Th1 cytokine profile by IL-12 coadministration achieves protective immunity. These data demonstrate a crucial role of Th1 responses in the control of hepadnavirus replication and suggest new approaches to inducing protection against HBV infection.