together at a relatively high density. In natural infec-SEE ARTICLE ON PAGE 205. tions, the presence of HCV 6 in macrophages [7][8][9] and Kupffer cells 10 suggests that Fc receptors, which bind In this issue of HEPATOLOGY, Shimizu et al. 1 build to a conserved portion of antibodies, may facilitate antibody-dependent entry into cells expressing Fc recep-on the foundation they helped to create, presenting electron micrographs of 50 nm virus-like particles in a tors. Yields of flaviviruses, which are in the same family as HCV, are increased up to 1,000-fold if the virus is liver sample from a hepatitis C virus (HCV) infected chimpanzee and in the cytoplasms of two types of tissue mixed with subneutralizing concentrations of antiviral antibodies before incubation with cells bearing Fc re-culture cells, a human T cell line used in previous investigations of HCV RNA replication, 2 and a human B-ceptors. 11 Further experiments are needed to determine whether Fc receptors are important for HCV in-cell line, Daudi lymphoblastoid cells. These longawaited images reveal that the morphological features fection and to seek alternate routes HCV might use to enter cells lacking Fc receptors. In the meantime, Fc of intracellular particles are similar to those of the 55 nm to 65 nm HCV particles previously described in receptors illustrate how the level of a particular cellular protein could influence HCV's cellular tropism. serum samples. [3][4][5] Immunoperoxidase staining, carried out with antibodies specific for a synthetic peptide rep-INSIDE A CELL, HCV REPLICATION IS resenting the HCV core protein and for a recombinant REGULATED version of the HCV envelope protein, was used to localize these HCV proteins in electron micrographs of the Viral expression is controlled by signals built into cultured cells.
the molecular biology of the virus and by cellular fac-Compared to the cultured cells, the liver samples tors. Just as the population of surface receptors differs contained very few virus-like particles. Among 18 liver between cell types, the level of cellular factors needed tissues evaluated by immunofluorescence, 10 from for viral replication may also differ. In the case of HCV, chimpanzees and 8 from humans, only the liver tissue the rate of viral protein synthesis appears to be regufrom 1 chimpanzee contained a high enough level of lated, in part, by positive 12 and negative 13 translational HCV proteins to be judged suitable for ultrastructural control elements in the 5 untranslated region of the analysis. Why do these non-hepatic lymphocyte-deviral messenger (mRNA). Cellular and viral proteins rived tissue culture cells provide a richer source of vimay switch these RNA control elements on and off. rus-like HCV particles than liver tissues?
Regulatory signals may be one way HCV handles the multiple demands placed on its pool of genomic RNA.