Is hepatitis C cytopathic?

There are a number of mechanisms whereby HCV could trigger liver cell injury during infection (Table 5.1). Injury could be triggered directly by the virus (i.e., a cytopathic effect) and/or by immune responses against virus-infected cells. HCV-associated liver cell injury could also result from the interactions of HCV with a variety of environmental agents, some of which are mentioned below. Flaviviruses are often cytopathic (Chambers et al., 1990) in that they damage or destroy the cells in which they are growing; consequently it was initially thought that the related HCV might also be cytopathic (Table 5.2). Some evidence has supported such a cytopathic effect whereas other studies have suggested that HCV is not cytopathic. Cell damage was observed with a minimal inflammatory response in monkeys experimentally infected with selected flaviviruses (Monath, 1990). Early studies with NANBH showed cell rounding, shrinkage, and nuclear pyknosis, which are characteristic, cytopathic effects. Damage was also observed in the membranes of mitochrondria and ER (Omata et al., 1981; Dienes et al., 1982). Following the discovery of HCV, it was shown that HCV RNA in the liver, but not in serum, was associated with severe inflammation (Lau et al., 1993). The likelihood that HCV maturation and replication is membrane associated may provide an explanation for the membrane alterations in HCV infection.