HCV Regulation of Host Defense
ABSTRACT Mammalian cells respond to virus challenge by initiating a “host response” characterized by interferon α/β (IFN) production and a cellular antiviral state. The host response is our first line of immune defense against viral pathogens and it imposes several barriers that hepatitis C virus (HCV) must overcome to replicate and persist. HCV evades the host response through a complex combination of virus-host interactions that disrupt intracellular signaling pathways and attenuate the antiviral actions of IFN. Regulation of the host response breaks a link between innate and adaptive immunity and provides a foundation for HCV replication and spread.
Article: Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.[show abstract] [hide abstract]
ABSTRACT: Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and in situ synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the in vivo behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments.PLoS ONE 01/2012; 7(7):e42100. · 4.09 Impact Factor