In:
eLife, eLife Sciences Publications, Ltd, Vol. 1 ( 2012-11-13)
Abstract:
Liver diseases related to the human hepatitis B virus (HBV) kill about 1 million people every year, and more than 350 million people around the world are infected with the virus. Some 15 million of these people are also infected with the hepatitis D virus (HDV), which is a satellite virus of HBV, and this places them at an even higher risk of liver diseases, including cancer. The viruses are known to enter liver cells by binding to receptors on their surface before being engulfed. Both HBV and HDV have outer coats that consist of three kinds of envelope proteins, and a region called the pre-S1 domain in one of them is known to have a central role in the interaction between the viruses and the receptors and, therefore, in infecting the cells. However, the identity of the HBV receptor has remained a mystery. Now Yan et al. have identified this receptor to be sodium taurocholate cotransporting polypeptide. This protein, known as NTCP for short, is normally involved in the circulation of bile acids in the body. In addition to humans, only two species are known to be susceptible to infection by human HBV and HDV—chimpanzees and a small mammal known as the treeshrew. Yan et al. started by isolating primary liver cells from treeshrews, and then used a combination of advanced purification and mass spectrometry analysis to show that the NTCP on the surface of the cells interacts with the pre-S1 domain in HBV. The authors then performed a series of gene knockdown experiments on liver cells of both human and treeshrew origin: when the gene that codes for NTCP was silenced, HBV infection was greatly reduced. Moreover, they were able to transfect HepG2 cells—which are widely used in research into liver disease, but are not susceptible to HBV and HDV infection—with NTCP from humans and treeshrews to make them susceptible. Similarly, although monkeys are not susceptible to HBV, replacing just five amino acids in monkey NTCP with their human counterparts was enough to make the monkey NTCP a functional receptor for the viruses. In the past, basic research into HBV and the development of antiviral therapeutics have both been hindered by the lack of suitable in vitro infection systems and animal models. Now, the work of Yan et al. means that it will be possible to use NTCP-complemented HepG2 cells for challenges as diverse as fundamental studies of basic viral entry/replication mechanisms and large-scale drug screening. It is also possible that HBV and HDV infection might interfere with some of the important physiological functions carried out by NTCP, so the latest work could also be of interest to medical scientists working on other diseases related to these infections.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00049.001
DOI:
10.7554/eLife.00049.002
DOI:
10.7554/eLife.00049.003
DOI:
10.7554/eLife.00049.004
DOI:
10.7554/eLife.00049.005
DOI:
10.7554/eLife.00049.006
DOI:
10.7554/eLife.00049.007
DOI:
10.7554/eLife.00049.008
DOI:
10.7554/eLife.00049.009
DOI:
10.7554/eLife.00049.010
DOI:
10.7554/eLife.00049.011
DOI:
10.7554/eLife.00049.012
DOI:
10.7554/eLife.00049.013
DOI:
10.7554/eLife.00049.014
DOI:
10.7554/eLife.00049.015
DOI:
10.7554/eLife.00049.016
DOI:
10.7554/eLife.00049.017
DOI:
10.7554/eLife.00049.018
DOI:
10.7554/eLife.00049.019
DOI:
10.7554/eLife.00049.020
DOI:
10.7554/eLife.00049.021
DOI:
10.7554/eLife.00049.022
DOI:
10.7554/eLife.00049.023
DOI:
10.7554/eLife.00049.024
DOI:
10.7554/eLife.00049.025
DOI:
10.7554/eLife.00049.026
DOI:
10.7554/eLife.00049.027
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2012
detail.hit.zdb_id:
2687154-3
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