609 BASELINE CHARACTERISTICS AND WEEK-4 RESPONSE AMONG 1546 CHC PATIENTS INFECTED WITH HCV GENOTYPE 1, 2, 3 AND 4: INTERIM RESULTS OF THE PROPHESYS COHORT

Abstract

The mechanism of innate immune response to the hepatitis C virus (HCV) has not been fully elucidated, largely due to the lack of an appropriate model. We examined the innate immune response to the HCV structural proteins using HCV transgenic (Tg) mice, which express core, E1, E2, and NS2 proteins, regulated by the Cre/loxP switching expression system. The level of HCV core protein was 15-47 pg/mg of total protein in the HCV Tg mice livers at 12 h after the HCV transgene expression. In contrast, we found a high level of expression of HCV core protein (1597 pg/mL) in transgenic mice with a large depletion of natural killer (NK) cells. Cre-mediated genomic DNA recombination efficiency in the HCV Tg mice was was strongly observed in NK cell depleted mice, compared to non-treated mice between 0.5 and 1 day.These data indicated that in the early naive immune responses the NK cells have important roles in initial recognition of HCV protein and the later elimination of core expressed hepatocytes.