Hepatitis C virus is one of several viruses that can cause hepatitis. It is unrelated to the other common hepatitis viruses (A, B, D, and E). Hepatitis C virus is a member of the Flaviviridae family of viruses.

Viruses belonging to this family all have RNA as their genetic material. Therefore, they are referred to as RNA viruses. The RNA of hepatitis C virus is made up of almost 10,000 units called nucleotides that are organized to serve as the virus's genetic blue print for the manufacture of proteins. Thus, the virus contains structural proteins to build its structure, including its coat, and non-structural proteins (e.g., the enzyme polymerase) to carry out its functions. Understanding the nature of hepatitis C virus allows scientists to develop therapy that specifically targets the virus's structure or functions.
There are considerable differences in the genetic structure of hepatitis C virus. Accordingly, hepatitis C virus is categorized into six major genetic types (genotypes) and many more subtypes, based on order of nucleotides in the virus. Although the different genotypes are found throughout the world, there is a distinct distribution of genotypes in certain geographic regions. For instance, the most common genotype in the U.S. is genotype 1 (1a and 1b), which accounts for 80% of hepatitis C virus cases in the U.S.

The influence of genotype on the long-term prognosis of hepatitis C virus disease is still unclear. However, what is clear is that patients infected with genotypes 2 or 3 are much more likely to respond to interferon therapy. In contrast, patients infected with genotype 1 (particularly 1b) or genotype 4 do not respond very well to interferon therapy.

In addition, within a single host, there are minor genetic differences in the hepatitis C virus. These minor differences give rise to what are called quasispecies (quasi means resembling each other). Where do the quasispecies come from? Well, one of the non-structural hepatitis C virus proteins mentioned above is the enzyme polymerase. This enzyme is the machine that allows the virus to reproduce its genetic material (RNA) in order to multiply. Now, this RNA polymerase is very prone to making mistakes, resulting in changes in the genetic material. The majority of these mutations result in a non-viable new quasispecies of hepatitis C virus, but sometimes the mutation results in viable quasispecies. With time, the accumulation of these viable mutations results in multiple quasispecies of the virus within the same host.

Why are there so many different varieties of hepatitis C virus anyway? Perhaps the different varieties confer an advantage to the survival of this virus over the years. For example, some of the new species may become more efficient in replication. By the same token, however, the genetic variability of hepatitis C virus has made the development of a protective vaccine against all of these genotypes and quasispecies a near impossible task with our present technology. Moreover, this variability probably also explains how this virus results in such a high rate of chronic infection. Thus, the genetic variability may enable the hepatitis C virus to avoid destruction by the host's cellular immune cells or antibodies, and so maintain the chronic infection.