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The hepatitis C virus

HCV Virus

Compared to other viruses the hepatitis C virus (HCV) is very small. Until recently this has made it difficult to study.

It is transmitted through blood to blood contact and is highly infectious. It is extremely resilient and can even survive outside the body in tiny droplets of blood. Depending on conditions such as room temperature it can remain infectious from anywhere between sixteen hours and four days on surfaces and a few weeks inside a syringe.[1]

The virus is unstable and mutates frequently. This is why medical equipment and other tools which regularly come into contact with blood, such as tattooist’s guns, must be thoroughly sterilised after each use.

HCV is often described as an indolent virus. This means it is usually slow to establish itself and it can take time to cause chronic infection. As it is so unstable, it may make many copies of itself which do not survive. It may also be that many virus particles are neutralised by the immune system. This occurs at a slower rate than that of viral replication, so the virus still gains the upper hand, but only slowly.

[1] Accessed 13/03/2013 -

Categorisation of HCV

HCV bears little similarity to the hepatitis A virus or the hepatitis B virus, even though all three target the liver. It belongs to the Flaviviridae family of viruses, which includes viruses such as dengue fever and yellow fever, as well as the Japanese and tick-borne encephalitis viruses.

Like all Flaviviridae viruses, hepatitis C is an RNA virus. RNA and DNA viruses differ in the ways in which their genetic information is packaged. RNA viruses are much less stable than DNA viruses, making them much more prone to mutation. Some scientists now think that some of the differences in the copies RNA viruses make are actually intentional. This increases their genetic variation, improving their ability to survive. This problem solving technique is known as ‘genomic intelligence’.

This ability to mutate makes it much harder to design vaccines and create drugs to treat RNA viruses. As soon as they encounter drugs or vaccines the RNA viruses immediately begin looking for ways to overcome them. There is now evidence that mutation rates of HCV actually accelerate in response to interferon and ribavirin therapy.[2]

[2]Asahina Y, et al. Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J Hepatol. 2005 Oct;43(4):623-9. Accessed on 13/03/2013,

Genotypes of HCV

The ability of the virus to mutate has resulted in the existence of different genetic variations of HCV. These are called genotypes. The different genotypes are often, but not exclusively, related to different parts of the world.

Genotypes 1, 2 and 3 have a worldwide distribution. Types 1a and 1b are the most common, accounting for about 60% of global infections. They predominate in Northern Europe and North America and in Southern and Eastern Europe and Japan. Genotype 2 is less frequently represented than type 1. Genotype 3 is endemic in south-east Asia. Genotype 4 is principally found in the Middle East, Egypt, and central Africa. Type 5 is almost exclusively found in South Africa[3]. The most common genotypes found in the UK are 1 and 3.

[3] World Health Organization. Hepatitis C: The hepatitis C virus. Accessed on 14/03/13 at:

Genotype map

It is still unclear whether or not the type of virus affects the progression of the disease. If it does it is not thought to present any real cause for concern. However, HCV genotype does influence response to treatment. If you are considering treatment it is very important to know which genotype (and ideally the subtype) you are actually infected with.

Each genotype also contains a series of minor variations. These are known as ‘subtypes’. They are numbered a,b,c,d etc., in order of their discovery. A person chronically infected with hepatitis C will have a viral population consisting of a very large quantity of these minor genetic variations. These are called ‘quasi species’ and present an even more complex problem for the immune system to deal with.

HCV is also described as having positive-sense, single-stranded RNA genomes. This means that each viral particle contains a single RNA strand. Within HCV the RNA has two functions. Firstly, it holds the information about HCV genetics. Secondly, it also contains information about how to make the proteins the virus needs for replication, both from its own components and from those of the host liver cell.

HCV's journey through the body

Once it is has gained access to the human body the hepatitis virus enters the blood stream. Then it seeks out cells which will let it in. When it has found and entered these cells it can then begin to reproduce.

It was originally thought that HCV only infected liver cells. This is now known not to be correct. The virus is also found in parts of the immune system, in bone marrow cells and in cerebrospinal fluid. However, the liver cells are the ones which the virus primarily targets.

Once the virus reaches the liver it attaches itself to receptors on the outside of its cells. The proteins encasing the virus confuse the receptors so that they cannot recognise it as a danger. The receptors consequently allow the virus into the cell. Once inside, the virus sheds its protein shells. The virus then unravels itself releasing instructions to build up new protein structures using its own components and those of the host cell.

The RNA genome reproduces itself and then reassembles around the newly made protein shells forming a new, protected virus particle. It is now ready to break out of the cell and infect others. Normally when cells are infected by viruses they immediately begin to self destruct. They then release a type of interferon that instructs all nearby cells to do the same to prevent the virus from spreading. However, like many other viruses, HCV has developed ways of interfering with this process. In doing so it dramatically increases its chances of surviving and thriving.

Obstacles to HCV Research

The exact nature of these complex processes is still far from fully understood. A vaccine will be difficult to produce until we know more about the virus. So far scientific research has been hampered by two major obstacles.

Firstly, until very recently it had not been possible to develop an efficient cell culture system of HCV in the laboratory. Progress in research now means that the last part of the virus life cycle - viral replication, assembly and release from the host cell – can now begin to be studied.

Another model system is still needed to show the beginning stages of the virus life cycle. Until this is possible, questions such as how HCV enters host cells, and how it behaves in the cell before it replicates, cannot be answered

The second obstacle is the lack of an animal model. The chimpanzee is virtually the only species besides humans susceptible to HCV infection. As a primate it would provide particularly useful information because of its genetic similarity to humans. However, as chimpanzees are an endangered species, they are very expensive to use, not to mention the ethical issues associated with this type of research.