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From blank round to a potently active substance?
Date:4/19/2013

differing mechanism of action

Prof. Hornung believed that the lack of transferability between mice and humans might be associated with the specific target structures that CMA latches on to. The team working with Prof. Hornung was then able to identify the protein to which CMA attaches, its receptor, in mouse cells. However, the human counterpart of this receptor did not respond to CMA. When CMA binds to the receptor in mice, a signal cascade is set into motion that leads to the release of interferons which in turn boost the immune system. However, in order for this to work, CMA and its receptor must fit together like a lock and key. Together with the laboratory of Prof. Dr. Karl-Peter Hopfner from the Gene Center at the Ludwig Maximilian University in Munich, the team from the Bonn University Hospital investigated the receptor variants of mice and humans in cell cultures and as purified proteins.

Animal models cannot easily be transferred to humans

"A few small differences in the receptor make the active substance completely ineffective in humans," reports lead author Taner Cavlar, postgraduate in Prof. Hornung's team. In humans, this prevents CMA from being able to latch its crucial receptor and release interferon, even though immune stimulation occurs in mice. "This is an example of the fact that results from animal models cannot always be easily transferred to humans," says Prof. Hornung. "Comparative investigations on human cells should take place at an early stage of active substance development."

Findings inspire the search for an antiviral drug

Since the scientists were able to figure out the exact structure of the mouse and human receptors, they now have an approach to see if there are conditions under which CMA could also arm the human immune system to fight viruses. This is now the next step which the researchers want to address with their colleagues. However, it will likely take many years u
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Contact: Dr. Veit Hornung
veit.hornung@uni-bonn.de
49-228-287-51200
University of Bonn
Source:Eurekalert

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