Adenovirus recombinantes frente a la infección por el virus de la hepatitis cpotenciación de la respuesta inmunitaria antiviral y bloqueo de las acciones inmunisupresoras del virus

Zusammenfassung

Titulo: Adenovirus recombinantes frente a la infección por el virus de la hepatitis c potenciación de la respuesta inmunitaria antiviral y bloqueo de las acciones inmunisupresoras del virus Resumen: Hepatitis c virus (hcv) induces chronic infection in 80% of infected individuáis, which can lead to cirrhosis and hepatocellular carcinoma, strong and persistent CD8+ and CD4+ t-cell responses are associated with viral clearance. The high levies of chronicity suqgest that the virus has developed several mechanisms to escape immune surveillance. In this work we have studied the capacity of different immunogens (recombinant adenoviruses expressing different proteins of the HCV or CD40 ligand, plasmid DNA, recombinant proteins, a recombinant Semliki forest virus (SFV) or anti-CDl37 monoclonal antibodies) to induce anti-HCV immune responses. These strategies were tested on their capacity to protect mice against infection with a recombinant vaccinia virus expressing HCV polyprotein which we used as a surrogate for HCV infection. It was found that recombinant adenovirus alone, or combined with anti-CDl37 monoclonal antibodies or with SFV, protects mice against HCV-recombinant vaccinia virus infection. it has been described that HCV core protein might inhibit several signalling pathways.Thus, we investigated if an adenovirus encoding HCV core and El (RAdCEl) could reduce liver cell injury in different in vivo models of fulminant hepatitis, it was found that RAdCEl markedly attenuated hepatocellular apoptosis as well as the levies of transaminases in sera after concanavalina A or anti-Fas antibody administration. These effects of HCV core protein might represent a mechanism favoring viral persistence