Hepatitis C virus


 * This page is for the virus. For the disease, see Hepatitis C.

The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus in the family Flaviviridae. Although hepatitis A, hepatitis B, and hepatitis C have similar names (because they all cause liver inflammation), these are distinctly different viruses both genetically and clinically.

Replication
Replication of HCV involves several steps. The viruses need a certain environment to be able to replicate, and therefore first has move to such areas.

HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, HCV also has an exceptionally high mutation rate, a factor that may help it elude the host's immune response.

Location
HCV mainly replicates within hepatocytes in the liver, although there is controversial evidence for replication in lymphocytes or monocytes. By mechanisms of host tropism, the viruses reach these proper locations. Circulating HCV particles bind to receptors on the surfaces of hepatocytes and subsequently enter the cells. Two putative HCV receptors are CD81 and human scavenger receptor class B1 (SR-BI). However, these receptors are found throughout the body. The identification of hepatocyte-specific cofactors that determine observed HCV liver tropism are currently under investigation.

Biosynthesis
Once inside the hepatocyte, HCV initiates the lytic cycle. It utilizes the intracellular machinery necessary to accomplish its own replication. Specifically, the HCV genome is translated to produce a single protein of around 3011 amino acids. This "polyprotein" is then proteolytically processed by viral and cellular proteases to produce three structural (virion-associated) and seven nonstructural (NS) proteins. Alternatively, a frameshift may occur in the Core region to produce an Alternate Reading Frame Protein (ARFP). HCV encodes two proteases, the NS2 cysteine autoprotease and the NS3-4A serine protease. The NS proteins then recruit the viral genome into an RNA replication complex, which is associated with rearranged cytoplasmic membranes. RNA replication takes places via the viral RNA-dependent RNA polymerase of NS5B, which produces a negative-strand RNA intermediate. The negative strand RNA then serves as a template for the production of new positive-strand viral genomes. Nascent genomes can then be translated, further replicated, or packaged within new virus particles. New virus particles presumably bud into the secretory pathway and are released at the cell surface.

Types
Based on genetic differences between HCV isolates, the hepatitis C virus species is classified into six genotypes (1-6) with several subtypes within each genotype. Subtypes are further broken down into quasispecies based on their genetic diversity. The preponderance and distribution of HCV genotypes varies globally. For example, in North America, genotype 1a predominates followed by 1b, 2a, 2b, and 3a. In Europe, genotype 1b is predominant followed by 2a, 2b, 2c, and 3a. Genotypes 4 and 5 are found almost exclusively in Africa. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6). Duration of standard interferon-based therapy for genotypes 1 and 4 is 48 weeks, whereas treatment for genotypes 2 and 3 is completed in 24 weeks.

Vaccination
Unlike hepatitis A and B, there is no vaccine to prevent hepatitis C infection.

In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.

Current Research
In 2007 the World Community Grid launched a project where by computer modeling of the Hepatitis C Virus (and related viruses) thousands of small molecules are screened for their potential anti-viral properties in fighting the Hepatitis C Virus. This is the first project to seek out medicines to directly attack the virus once a person is infected. This is a distributed process project similar to SETI@Home where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering the Hepatitis C Virus is called "Discovering Dengue Drugs – Together." The software and information about the project can be found at:


 * World Community Grid web site