News archive 2008
New protein discovered to block HIV18 Jan 2008, PR 14/08
The discovery of a novel human protein called tetherin which appears to block the replication of HIV-1 thereby halting the spread of the virus, has been made by Dr Stuart Neil, Lecturer in the Department of Infectious Diseases at King’s College London.
Dr Neil isolated tetherin whilst working in the group of Paul Bieniasz at Rockefeller University’s Aaron Diamond AIDS Research Center in New York. This breakthrough study published in Nature is particularly exciting because tetherin might be an important antiviral inhibitor of many diverse viruses.
Lead researcher Dr Stuart Neil and a team of researchers in the Infectious Disease Department at King’s will set up a laboratory to focus on trying to understand the mechanisms by which the HIV-1 gene Vpu counteracts tetherin. Dr Neil comments; ‘With this new discovery there is potential for opening up a novel drug target for the treatment of HIV/AIDS. Understanding how Vpu takes out the activity of Tetherin will facilitate the design of therapeutics to inhibit this part of the virus, allowing the cell’s natural defence systems to interfere with HIV replication.' The research will be funded by the Wellcome Trust.
HIV-1, the virus responsible for the AIDS pandemic, encodes several small proteins whose role is to subvert host mechanisms that block viral replication. One protein, termed Vpu, is known to overcome a factor in infected human cells that interferes with the release of new HIV-1 virus particles. This novel protein tetherin appears to block the replication of HIV-1 that lacks a Vpu gene by keeping newly produced viral particles stuck to the surface infected cells, and preventing the spread of the virus.
The HIV protein Vpu is required for the release of viral particles, and evidence for a tetherin molecule has accumulated over the last few years. Paul Bieniasz and colleagues show that Vpu works to neutralize the host cell protein CD317, which they rename tetherin. In this way it allows efficient discharge of HIV-1 particles from infected cells. The team argue that inhibition of virus release by tetherin is a previously unknown mechanism by which organisms protect themselves against certain viruses. (Nature Press Release)
In the absence of a Vpu gene, the production of HIV-1 from human cells is inefficient because a human factor prevents the release new viral particles, leaving them stuck on the cell surface. This effect is far more pronounced when cells are treated with Interferon, a protein released from virally infected cells that tells the surrounding tissue to shut-down virus replication.
Dr Neil explains: ‘We isolated tetherin by looking for genes in human cells that were induced by interferon. Tetherin is a protein found in the cell membrane whose function was until now unknown. We showed that expression of tetherin was sufficient to block the replication of HIV-1 that lacked a Vpu gene, but a functional Vpu protein negated tetherin’s effect. Thus we believe HIV-1 encodes Vpu as a way of getting round the antiviral effects of Tetherin. Understanding the mechanism by which Vpu does this may allow us to design drugs that inhibit its function, allowing Tetherin again to block HIV release, and suppress the ability of the virus to spread to new cells.’
The paper Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu is available online.
Notes to editors
Figure 1. In the absence of Vpu, expression of Tetherin causes newly made HIV-1 particles to remain stuck on the surface of infected cells, preventing their spread to new uninfected cells
King's College London
King's College London is one of the top 25 universities in the world (Times Higher 2007) and the fourth oldest in England. A research-led university based in the heart of London, King's has 19,300 students from more than 130 countries, and 5,000 employees. King's has an outstanding reputation for providing world-class teaching and cutting-edge research. The College is in the top group of UK universities for research earnings and has an annual income of approximately £400 million. An investment of £500 million has been made in the redevelopment of its estate.
King's has a particularly distinguished reputation in the humanities, law, social sciences, the health sciences, natural sciences and engineering, and has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA. It is the largest centre for the education of healthcare professionals in Europe and is home to five Medical Research Council Centres – more than any other university.
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