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Open Access Genome packaging of molecular mechanism in hepatitis C virus particle formation

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Hepatitis C is an infectious disease, leading to cirrhosis of the liver and hepatocellular carcinoma. It is estimated that 71 million people are infected with the hepatitis C virus (HCV), with around 400,000 dying from the disease each year. It is a bloodborne virus that must be introduced directly into the bloodstream. It is most commonly transmitted between intravenous drug users and in medical situations where transplanted blood is not screened and equipment not properly sterilised. It is therefore a serious concern amongst certain subpopulations and warrants thorough investigation. Currently, there are several treatments for HCV. These include combinatorial treatment with NS3/4A inhibitors, NS5A inhibitors and NS5B inhibitors, all of which inhibit viral replication. Treatment is typically 90 per cent successful, however whether the occurrence of liver cancer can be reduced in HCV-infected cirrhotic patients with sustained viral response is highly debatable. Development of new generation therapies, which are effective in the management of difficult-to-treat patients such as severe renal failure, as well as of pan-genotypic drugs for all HCV genotypes with minimal side effects, is expected. Additionally, many of those with HCV do not know their diagnosis and therefore the global treatment rate remains at around 13 per cent. Whilst some of the molecular processes behind this cycle are known, much remains a mystery. Primarily, it has long been unclear how HCV packages its genome into the viral particle. Investigating this and other unknowns concerning the virus is Professor Tetsuro Suzuki of the Hamamatsu University School of Medicine, Japan. As he explains: 'In general, viral RNA represents only a small fraction of the RNA molecules in the cells infected with RNA viruses, but the viral genomic RNA is considered to be selectively packaged into virions. Although evidence regarding the viral replication and particle formation of HCV are accumulating due to development of the HCV cell culture system, detailed mechanisms for incorporation of the viral genome into progeny virus particles has remained largely unclear. Our project has contributed, and continues to contribute to the understanding of the molecular mechanism of the process.'
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Keywords: COMBINATORIAL TREATMENT WITH NS3/4A INHIBITORS; HCV-INFECTED CIRRHOTIC PATIENTS; HEPATITIS C; HEPATOCELLULAR CARCINOMA; INHIBIT VIRAL REPLICATION; LIVER CANCER; NEW GENERATION THERAPIES; NS5A INHIBITORS AND NS5B INHIBITORS; PAN-GENOTYPIC DRUGS; PARTICLE FORMATION; VIRAL REPLICATION; VIRAL RNA; VIRUS PARTICLES

Document Type: Research Article

Publication date: October 15, 2018

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