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Hepatitis C virus causes both short-term illness and chronic liver disease leading to cirrhosis and cancer. Learn about the virus and how it replicates.

Hepatitis C

Your liver performs many essential functions like clearing the toxins out of the blood and making bile, which gets rid of waste and fats during digestion.

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Damage to your liver prevents it from carrying out these tasks and leads to many harmful substances building up in your body.Inflammation of the liver is known as hepatitis and can be caused by alcohol, drugs, and infection with bacteria or viruses. There are several types of hepatitis viruses, so named because of the similar symptoms they cause, though they are very different in their structure and replication.

While there are now vaccines to prevent both Hepatitis A and Hepatitis B, there is no vaccine for the Hepatitis C virus.This disease is a major global health problem causing an estimated half a million deaths per year. There are also an estimated 170 million people living with the virus. Many of these people could be cured using antivirals, drugs which specifically target the virus, but many people don’t realize they are infected or can’t afford the expensive treatments.Hepatitis C is spread mainly through blood, though sometimes it can be sexually transmitted. Before widespread screening of donors, people became infected from blood transfusions or organ donations.

The most common way to get infected these days is by using unsterilized medical equipment, like sharing needles to use illegal drugs or getting a tattoo.

Acute and Chronic Infections

Hepatitis C virus can cause two types of infections: acute and chronic. An acute infection means it lasts for only a short time. A chronic infection, however, means that the virus stays in the body long-term. Acute Hepatitis C can occur within the first 6 months of being infected with the virus. Most people do not have any symptoms during this period, so they have no idea they have the virus.

Those that do feel sick typically complain of joint pain, fever, vomiting, fatigue, and a yellowing of the eyes known as jaundice.About 20% of people infected with Hepatitis C will be able to get over the infection and their immune systems will be able to clear all of the viruses from the body. The rest of the people will go on to develop chronic Hepatitis C. For most of their lives, they will probably show no signs of illness and have no idea they are sick. The virus causes liver damage very slowly over years or even decades, similar to the liver damage caused by alcoholism.

Most people do not realize they have the virus until they are diagnosed with some sort of liver disease. Many develop cirrhosis of the liver, which means that their healthy liver tissue has been replaced with scar tissue. Once this damage has happened it can’t be reversed and prevents the liver from functioning normally. People with Hepatitis C also have an elevated risk of developing liver cancer.

In severe cases, the person will need a liver transplant to survive.

Viral Structure and Replication

Hepatitis C virus has an outer envelope containing two viral envelope proteins: E1 and E2. Underneath the membrane is a layer of the viral core protein, which binds to the viral genome forming the nucleocapsid where the RNA is located.

You can think of it like a capsule (‘-capsid’) that holds nucleic acid (‘nucleo-‘), in this case RNA. The viral genome of Hepatitis C virus is a single-stranded RNA that encodes 11 proteins.

Hepatitis C viral structure
hepatitis c structure

The primary cells infected by Hepatitis C virus are liver cells called hepatocytes.

The viral envelope proteins recognize markers on the surfaces of these cells. This causes the cell to fold its membrane inward, taking the virus up into a small pocket known as an endosome. It’s a little like Pac-Man eating a dot, where the liver cell is Pac-Man, and the endosome is the mouth of Pac-Man, which eats the dot, the virus.

Only this dot doesn’t disappear.Once inside the cell, the viral membrane fuses with the endosome membrane releasing the viral nucleocapsid into the cell cytoplasm. The viral RNA genome is similar to the cell’s messenger RNA (mRNA) so it can be translated by ribosomes in the cell’s endoplasmic reticulum. The long stretch of viral RNA is translated into one long protein, a polypeptide, with all the viral proteins strung together.

Hep C virus replicating within a liver cell.

hec c replication

Both cellular and viral enzymes known as proteases are needed to cut apart this long protein into the smaller functional ones. This produces the other nonstructural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B) that play important roles in the complex life cycle of this virus.Both viral proteins (like NS4A) and cellular proteins and membranes are used to set up viral replication complexes in the cytoplasm. These complexes rearrange things in the cell to make viral production more efficient. You can think of this like setting up an assembly line in a factory.

In these complexes, the viral RNA is copied by NS5B. This protein is an RNA-dependent RNA-polymerase, which means it uses RNA as a template to make more RNA. This is in contrast to human RNA polymerases, which typically use DNA as a template to make cellular mRNA.

The NS5B polymerase is helped by NS3, which binds to the viral single-stranded RNA and keeps it from folding up on itself. The viral replication complexes make the new viral genomes and viral proteins, which can then gather into new viruses to be exported out of the cell.

Lesson Summary

Inflammation of the liver, or hepatitis, can be caused by infections or things like drinking too much alcohol. One major cause of liver disease is Hepatitis C virus.

It is a serious global health problem and there is no vaccine to prevent it. The virus can cause an acute infection or stay in the body for years causing a chronic infection. Over time, the virus causes liver damage leading to cirrhosis or liver cancer. The virus infects hepatocytes, which are important cells in the liver.

Once the virus gets inside the cell’s cytoplasm, it sets up replication complexes made of both viral and cellular proteins. These complexes are used to speed up the process of making new viruses.

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