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Viral infections: Identifying the tell-tale patterns
Date:4/24/2014

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have identified the structural features that enable the innate immune system to discriminate between viral and endogenous RNAs in living cells.

When viruses infect cells, they take control of cellular metabolism and hijack cellular resources for the production of viral proteins. This process is dependent on viral RNA molecules that are delivered directly to (in the case of RNA viruses) and/or newly synthesized in the host cell, and provide the blueprints for the fabrication of viral proteins by the cell's translational apparatus. However, cells possess defense systems that are activated by specialized sensors that can distinguish viral RNAs from host RNAs. These proteins, three of which belong to the family of RIG-I like receptors (or RLRs), recognize and bind specifically to foreign RNAs. This in turn alerts the innate immune system, which proceeds to destroy the foreign RNAs, thus preventing the production of new virus particles. "Based on in-vitro experiments, it is known that RLR proteins bind to certain characteristic patterns in viral RNAs, but it had not been possible to isolate the precise RNA sequences bound by these proteins in living, virus-infected cells," says Professor Karl-Peter Hopfner of LMU's Genzentrum.

Tethering RNA to proteins with UV light

Hopfner, in collaboration with his colleagues Karl-Klaus Conzelmann (LMU), Johannes Sding (LMU) and Adolfo Garca-Sastre (Mount Sinai Hospital, New York), made use of a clever experimental strategy to get around this problem, which enabled them to purify and characterize ribonucleoprotein complexes containing viral RNAs from virus-infected cells. The intrinsic stability of the interaction between RLRs and viral RNAs is very low. So the researchers first had to stabilize the complexes in order to isolate them intact. For this purpose, they infected cells with measles virus, and incubated them in the presence of a ch
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Contact: Luise Dirscherl
presse@lmu.de
49-892-180-3423
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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