Monday, 4 August 2014

towards a high-resolution understanding of hepatitis C virus

HCV virions
Viruses are sub-microscopic parasites of cells. What this means is that despite our immense interest in them, they are very difficult to observe and study using your eyes or even traditional light microscopy, which is the mainstay of biology over the last few centuries. This is annoying because we are interested in understanding what viruses look like because of what they tells us about their biology as virus particle structure affects many aspects of its lifecycle, such as cell entry, replication and transmission. 

These questions are no more interesting than for HCV, an important human pathogen that has chronically infects between 130 and 150 million people worldwide and leads to between 350,000 and 500,00 deaths a year. Infection often lead on to chronic hepatitis, cirrhosis, fibrosis, hepatocellular carcinoma and eventually liver failure and death. Although there are now effective drugs targeting HCV, HCV and associated diseases are likely to continue to be a public health issue in the future because of their prohibitive cost. We do not yet have an effective vaccine to protect against the virus either. 

One avenue to aid development of antivirals and vaccines is to understand HCV particle (virion) structure and the pathways that promote its assembly and its entry into cells. The catch is that HCV has been extremely challenging to manipulate in the lab under experimental settings. However, a paper published in the journal PNAS, (free here from the Charles Rice lab in New York (first author: Maria Teresa Catanese) has shown the characterisation of HCV virion structure using a powerful microscopic technique: cryoelectron tomography (cryo-EM), which has improved our understanding of HCV biology. The continuing use of this imaging technology combined with models of HCV entry and assembly may aid in the development of novel HCV drugs and vaccines.