The chapters of this book have provided a multi- and interdisciplinary outline of HCV. However, there is still so much more work that has to be done before the virus, its biology, and associated diseases are understood well enough to generate effective vaccines and new potent therapeutics. To this end, a sampling of outstanding questions in the field are presented below.

What are some of the implications of the physical heterogeneity of hepatitis C?

Various studies have shown the density of HCV to vary from 1.03 to 1.20 g/ml (Bradley et al., 1991; Carrick et al., 1992; Miyamoto et al., 1992; Hijikata et al., 1993b; Thomssen et al., 1993; Kanto et al., 1994; Choo et al., 1995; Nakajima et al., 1996; Yoshikura et al., 1996). Although this may result from differences in the types or quantity of viral polypeptide that make up different virus particles, it seems more likely that this physical heterogeneity may be contributed by the association of virus particles with different types and amounts of host cell and serum components. The findings that LDLs and immunoglobulins are associated with HCV particles of different densities, and that virus from different densities also differ in infectivity, suggest that the host–virus relationship that develops after infection depends, in part, upon the physical composition of the virus particles. For example, complexing of virus particles with immunoglobulins may limit virus spread and infection of susceptible hepatocytes following a bout of hepatitis.