The Pathogenesis of Hepatitis C Virus Vertical Transmission

To evaluate for the presence of HCV Core protein, HCV RNA and SPP in the placenta and fetal
membranes using paraffin-embedded sections and post-delivery specimens respectively. In
parallel, we will assess placental tissue for evidence of HCV infection using a novel in situ
hybridization technique and translate our in vitro findings to these in vivo samples.

Our overall hypothesis is that cytotrophoblasts at the maternal-fetal interface within the
placenta serve as a "barrier" that must be crossed during vertical transmission and that
cytotrophoblasts are permissive to HCV at a low level that may be enhanced under certain
conditions. By comparing the regulation of key steps in the intracellular life cycle of HCV
in cytotrophoblasts to highly permissive hepatocytes, significant differences in HCV
regulation should be revealed.

Based on our preliminary data, our working hypothesis is that HCV Core protein is
differentially processed in cytotrophoblasts compared to hepatocytes.