The hepatitis C virus (HCV) is one of the most important causes of chronic liver disease in the United States. It causes an estimated 10,000 to 12,000 deaths annually in the United States. It has always been an enigma in medical history.
Hepatitis C virus when not detected can proceed to advanced stage called liver cirrhosis or liver cancer. Due to its asymptomatic nature, it has always been a mystery in medical field. In rare cases symptoms may occur. But that will not be common for all the patients. Currently about 170 million people are affected by this disease world wide.
In general 'hepatitis' means swelling of the liver. The cause for this inflammation is mainly due to viral infections.
HCV is an enveloped virus with 9500 nucleotide single stranded RNA that encodes a single polyprotein, which is then processed by the host cell and virus-encoded proteases into many structural and non-structural proteins needed for the replication of the virus.
GENOME OF HCV:
The genome of HCV contains positive-sense RNA molecule approximately 9.6kb length. There is a non-coding region (NCR) of 324-341 nucleotides at the 5' end and a 3' NCR of variable length including a poly (U) tract. The 5' NCR contains IRES (Internal Ribosomal Entry Site) apparently similar in function (but not structure) to that of picornaviruses. Short Untranslated regions at the end of the genome are needed for the replication of the genome.
The nucleotide sequence of HCV is highly variable .All over the world HCV has been grouped into six main genotypes and many subtypes' based on the sequence data.
EVOLUTIONARY NATURE OF HCV:
Evolution means 'gradual change in which the organisms change in their phenotype over a long period of time in response to external environmental condition'. This is generally the Darwinian type of evolution. But in the case of HCV, this Darwinian type of evolution makes very little contribution to the genetic diversity.
In the case of HCV, it replicates due to the error prone nature of polymerase enzyme .This enzyme lacks proof reading mechanism. So HCV results in the production of defective viral variants. They don't survive for a long time, since they will undergo mutation continuously. The off springs will not be the exact copies of the parent viral strain. While performing evolutionary studies of this virus 5' Non coding region (NCR) is often taken for analysis because, it undergoes less mutation compared to other parts of the gene. Generally the virus undergoes mutation at an alarming rate of 106 nucleotides.
Hepatitis C virus exists as quasispecies. So, it's very difficult to develop a vaccine against it. A viral quasispecies is a group of viruses related by a similar mutation or mutations, competing within a highly mutagenic environment. That means the virus will undergo mutation very often leading to its survival in the host. Since HCV lacks proof reading mechanisms it results in the production of defective viral variants.
The virus undergoes mutation at the rate of 106 due to the lack of proof reading mechanism. The mutation results in the production of many variants of the virus. This is called as Quasispecies. So the virus can spread very quickly in the host.
Due to this nature it is very difficult a discover a correct medicine against this particular virus. If left untreated the virus may develop even into Liver Cirrhosis i.e., Liver Cancer.
Since the virus undergoes quick mutation it is very difficult to control. May be epitope based drug can be designed in future to cure this disease. Generally Ribavirin has been used as a drug for treating Hepatitis C virus. But it does not give a complete cure against the disease. Currently Scientists are trying to discover a drug against this virus.
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I am working in IP company as Junior Research Associate.