A breakthrough in understanding hepatitis C virus
It has been estimated that around 2% of the world’s population, approximately 170 million people, are infected with hepatitis C virus (HCV). Over 4 million people in the USA are infected with HCV, a prevalence rate of 1.6%. The peak prevalence of HCV infection occurs among people of 40 to 49 years of age and a history of injection drug use is the strongest risk factor. The UK Health Protection Agency’s annual reports on HCV estimate that in England and Wales around 4,500 people are suffering from severe liver disease due to chronic HCV infection, and that this could rise to around 7,000 by 2010. Over 200,000 UK residents have chronic HCV infection, but five out of six are unaware of this. It is believed that around 80% of UK HCV infections are linked to the use of injected drugs, and 50% of injecting drug users are infected with HCV.
The majority of cases of HCV infection give rise to an acute illness, but up to 80% may then develop into chronic hepatitis. Almost all patients develop a vigorous antibody and cell-mediated immune response which fails to clear the virus infection but may contribute to liver damage. Spontaneous resolution of chronic liver disease is very rare (<2%) and patients with chronic disease are at risk of developing hepatocellular carcinoma (HCC).
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So HCV is a pretty important virus, but it has not been the easiest virus to study. The virus only infects only humans and chimpanzees and effectively cannot be grown in the laboratory. Consequently, until now studies of this virus in animal models have been restricted to chimpanzees and to immunodeficient mice transplanted with human hepatocytes hampering understanding of the virus and drug development. A paper in the most recent edition of Nature identifies a host protein that is essential for HCV entry into cells (Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457: 882-886, 12 February 2009). If this protein could be introduced into cells by genetic manipulation, this might produce new models for the study of HCV infection, and manipulating the protein in humans might be a route to protection against the virus.
The newly-identified protein which plays a role in HCV cell entry is occludin (OCLN), a protein involved in forming the tight junctions between cells. The researchers showed that adding this protein to mouse cells makes them susceptible to infection with HCV. Several other HCV cell entry factors had previously been identified, including CD81, scavenger receptor class B type I and claudin-1 (CLDN1). The mouse versions of SR-BI and CLDN1 function at least as well as the human proteins in promoting HCV entry, but OCLN and CD81 must be of human origin to allow efficient infection of mouse cells. The identification of the essential cell entry factors for HCV is an important advance in efforts to develop new models to allow us to study and fight this virus.
Related:
- Hepatitis C Virus: a mountain to climb
- Viruses and Human Cancer
- Does the outcome of HCV infection vary with the infecting virus type?
Tags: Biology, Health, Medicine, Microbiology, Podcast, Science, Virology
