What seems reassuring statistically, is that according to the World Health Organisation, around 3% of people worldwide are affected severely by the Hepatitis C virus (HCV). A small percentage one may consider, however it equates to a very large quantity. Additionally, a large number of people may have not been diagnosed with the infection as the infection takes time to develop. This can only mean that the actual number of people affected chronically with HCV is much higher.
A Summary of HCV Transmission:
A blood-bourne infection, HCV is commonly transmitted through (vascular) medical operations, or through intravenous drug usage. There have been nationwide catastrophes in some countries where blood, contaminated by HCV, has been used for transfusions. The identification of the virus was too late, and many people were medically affected.
The origin of the spread of HCV is largely unknown, although many agree that it could have been initially spread by some kind of vector, a mosquito being a predictable example. It has been discovered that the virus can spread through sexual transmission, however blood-to-blood contact is seen as the most efficient method of the virus' transmission.
Above: Electron Micrograph of the Hepatits C Virus (HCV) isolated from cell culture (Wikipedia)
The Significance of the Viral Genome:
The HCV, as characteristic of many viruses, is able to mutate at a frequent rate, making it very difficult to develop a long-lasting vaccine. The length of its genome is relatively short at around 10000 nucleotides long. The primary reason for the rapid mutating of the HCV genome, is that unlike in humans, the HCV virus has no mechanisms in place to proof-read its own DNA. This frequency results in copying errors during the process of DNA replication. Combining this feature (or rather a lack of it), with HCV's ability to replicate at an extraordinary rate, results in many mutations in the viral DNA sequence.
To most people, a mutation is seen an event detrimental to the host organisms, however this isn't always the case. In viruses, due to the large number of mutations that occur, mutations can sometimes be advantageous. Therefore the virus is able to acquire a protein that serves valuable to virus, allowing it to survive in more extreme conditions. One application of this is that an advantageous mutation can cause a virus to the evade the host organism's immune response. The host's own cells may recognise the new viral proteins as 'self' and thus fail to identify the intruder.
As mentioned, the HCV constitutes many different strains, and there is scientific evidence of this. Comparing HCV genomes from around the world, where it has caused infection in the local population, has given scientists insight into the impressive genetic diversity of this virus. Such diversity is simply uncharacteristic of most organisms, take humans as an example: 'the difference between the DNA sequences of individual humans is less than 1%'. However no matter how genetically diverse the HCV is, liver disease still developed upon infection.
Scientists have managed to categorise the differences between HCV strains, and classify the different HCV genotypes. The seven major genotypes of HCV range from G1 to G7. Each strain is prominent in different areas of the globe:
- G1 - found in Africa (endemic - constant transmission rates) as well as parts of Europe, the USA and Japan (causes epidemics - greatly fluctuating transmission rates).
- G2 - found in Western Africa (endemic) and near Mexico
- G3 - found in Asia (endemic) - in and around Northern India
- G4 - found in (Central) Africa (endemic)
- G5 - found in (southern) Africa (endemic)
- G6 - found in (Eastern) Asia (endemic)
- G7 - found in (Central) Africa
Above: World map showing the distribution of various strains of HCV and relative proportions of different genome types in each area (Hepatitis C Education & Prevention Society)
What is intriguing is that worldwide medical data suggests that some strains of HCV are statistically easier to treat than others. Take G1 and G2 as examples. G1 is in fact the most common type of HCV in the UK and is notoriously difficult to eradicate, 'only 50% of G1-infected people are treated successfully'. However G2 induced Hepatitis seems easier to treat, with success rates as high as 80%.
Looking to the Future:
Recent developments in genome sequencing, drug synthesis and virology has enabled scientists to develop potential drugs to combat this deadly virus. In today's world however the HCV isn't the only significant threat to global health, with HIV/AIDS being a notable contender. The primary function of these new drugs is to inhibit particular stages of the viral life cycle, by targeting viral enzymes. This is a more virus-directed approach which contrasts greatly to old drugs, which only focused on increasing the strength and effectiveness of the host's immune system. Additionally, knowing the differences in the genotype between strains of HCV will enable scientists to develop drugs capable of destroying all strains in equal effectiveness.
So who will win this 'evolutionary arms race'?
References:
Credit to Dr Rebecca Gray PhD, who is studying the evolution of HCV and is now a research fellow at the University of Oxford for her original article on Hepatitis C published in the Biological Sciences Review (Volume 26, Number 1).
Additional credit - 'Hepatitis C - NHS Choices'. Read more.
(Image references are given in captions)
Further reading:
- The World Health Organisation provides more information on the Hepatitis C Virus. Read more
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