Life Cycle Of The Hepatitis C Virus

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The hepatitis C virus must attach to and infect liver cells in order to carry out its life cycle and reproduce - this is why it is associated with liver disease. While little is known about the exact natural processes of hepatitis C, like other viruses, it must complete eight key steps to carry out its life cycle:

1. The virus locates and attaches itself to a liver cell. Hepatitis C uses particular proteins present on its protective lipid coat to attach to a receptor site (a recognizable structure on the surface of the liver cell).

2. The virus's protein core penetrates the plasma membrane and enters the cell. To accomplish this, hepatitis C utlilizes its protective lipid (fatty) coat, merging its lipid coat with the cellÕs outer membrane (the coat is in fact composed of a fragment of another liver cell's plasma membrane). Once the lipid coat has successfully fused to the plasma membrane, the membrane engulfs the virus - and the viral core is inside the cell.

3. The protein coat dissolves to release the viral RNA in the cell. This may be accomplished during penetration of the cell membrane (it is broken open when it is released into the cytoplasm), or special enzymes present in liver cells may be used to dissolve the casing.

4. The viral RNA then coopts the cell's ribosomes, and begins the production of materials necessary for viral reproduction. Because hepatitis C stores its information in a "sense" strand of RNA, the viral RNA itself can be directly read by the host cell's ribosomes, functioning like the normal mRNA present in the cell. As it begins producing the materials coded in its RNA, the virus also probably shuts down most of the normal functions of the cell, conserving its energy for the production of viral material, although it occasionally appears that hepatitis C will stimulate the cell to reproduce (presumably to create more cells that can produce viruses), which is why hepatitis C is often associated with liver cancer. The viral RNA first synthesizes the RNA transcriptase it will need for reproduction.

5. Once there is adequate RNA transcriptase, the viral RNA creates an antisense version (the paired opposite) of itself as a template for the creation of new viral RNA. The viral RNA is now copied hundreds or thousands of times, making the genetic material for new viruses. Some of this new RNA will contain mutations.

6. Viral RNA then directs the production of protein-based capsomeres (the building blocks for the virus's protective protein coat). Ribosomes create the proteins and
release them for use.

7. The completed capsomeres assemble around the new viral RNA into new viral particles. The capsomeres are designed to attract each other and fit together in a certain way. When enough capsomeres are brought together, they self-assemble to form a spherical shell, called a capsid, that fully encapsulates the virus's RNA. The completed particle is called a nucleocapsid.

8. The newly formed viruses travel to the inside portion of the plasma membrane and attach to it, creating a bud. The plasma membrane encircles the virus and then releases it - providing the virus with its protective lipid coat, which it will later use to attach to another liver cell. This process of budding and release of new viruses continues for hours at the cell surface until the cell dies from exhaustion.

Each surviving virus - those which are not destroyed by the immune system or other environmental factors - can produce hundreds or thousands of offspring. Over time, this endless cycle of reproduction results in significant damage to the liver, as millions upon millions of cells are destroyed by viral reproduction or by the immune system's attacks on infected cells.

Dartmouth Medical School