Occult infection of peripheral B cells by hepatitis C variants which have low translational efficiency in cultured hepatocytes

BackgroundPlasma hepatitis C virus (HCV) originates from hepatocytes. However, in certain subjects, B cells may harbour both plasma strains and occult HCV strains tha t are not detected in the plasma. The internal ribosome entry site (IRES) of these latter strains is mutated, suggesting that the efficiency of viral translation could drive the cellular tropism of HCV.AimsTo determine if the translational efficiency of IRES variants in cultured hepatocytes or B cells is correlated with their cellular tropism in vivo.MethodsThe efficiency of IRES of 10 B cell-specific variants and nine plasma variants, isolated from six patients with compartmentalised variants in B cells, was estimated by bicistronic dual luciferase expression in hepatocyte cell types (Huh7), in primary cultured human hepatocytes (PCHs) and in two B cell lines (Raji and Daudi).ResultsFor each of the six subjects, the plasma IRESes were significantly and repeatedly more efficient than B cell IRESes in Huh7 (1.7±0.3 vs 0.7±0.2; p