Drug flags up virus-infected cells for destruction by the body's own immune system
A drug that flags up virus-infected cells for destruction by the body’s own immune system could lead to new, broad-spectrum anti-viral treatments, US scientists say.
A University of Texas Southwestern Medical Center-based team say their compound exploits a molecular ’flip’ that occurs in the membrane of host cells that have been infected by a wide range of viruses, including the flu virus, HIV, and viral bioterrorism agents.
The antibody-based drug, called bavituximab, recognises and binds to phosphatidylserine (PS) lipids, which are normally positioned on the internal surface of cells but are known to flip to the outside of cells activated to replicate or to die. Philip Thorpe and colleagues at UT Southwestern decided to test whether the same lipid flip would occur when cells were infected by a virus - which activates the cell to hijack its replicative machinery - and whether this could be exploited by a drug.
The team infected guinea pigs with Pichinide virus, similar to the human Lassa fever virus, which is endemic in parts of Africa and classed as a bioterrorism agent. While all the untreated guinea pigs died, half the animals treated with bavituximab recovered, suggesting that the virally infected cells were being tagged by the antibody, then recognised and destroyed by the immune system. ’In the case of virus infection, the binding raises a red flag to the body’s immune system, forcing the deployment of defensive white blood cells to attack the infected cells,’ says Thorpe.
’It could very well be that this is a generic feature of enveloped viruses,’ adds Melina Soares, Instructor of Pharmacology at UT Southwestern and lead author of the study. ’It could lead to a new, broad spectrum anti-viral treatment.’
According to Thorpe, around 99 per cent of current anti-viral drugs target properties that are encoded by the virus. But this new approach targets a feature of the infected host cell that isn’t controlled by the virus, so viral resistance to the drug is unlikely to emerge from viral mutations.
Clinical trials are underway to treat hepatitis C patients with bavituximab, which show promise of being safe and effective at reducing patient blood-virus levels. Thorpe told Chemistry World that a treatment might be available in five years.
But Patricia Spear, Professor of Microbiology-Immunology at the Feinberg School of Medicine, Northwestern University, Chicago, points out a possible limitation. ’This antibody will probably be effective for short-term use but what about long-term use in chronic infections such as that caused by hepatitis C? I suspect the antibody will induce an immune response during long-term use and become ineffective,’ she says.
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M M Soares, S W King and P E Thorpe, Nature Medicine, 2008, DOI: doi:10.1038/nm.1885