Viruses are obligate parasites and can only reproduce within host cells because they lack metabolic pathways to complete their replication cycles. Host factors required in viral replication are mainly those involved in lipid metabolism, cell cycle control and apoptosis, cell-to-cell interactions, immune system regulation, etc. Several inhibitors targeting viral polymerases have been designed. However, the rapid appearance of resistant mutants, as a direct consequence of the viral population structure, diminishes the efficacy of this kind of molecules. To elude the rapid loss of treatment efficiency due to the appearance of resistance mutations, cellular factors have been proposed as a promising therapeutic target to inhibit RNA(+) virus replication. In this review, we focus on those interactions between host factors and HCV replicase, to modulate either cellular metabolism or HCV polymerase activity.
