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Sci. Signal., 12 February 2013
Vol. 6, Issue 262, p. ec43
[DOI: 10.1126/scisignal.2004045]


Immunology Parainfluenza 5 and MDA5

Kristen L. Mueller

Science Signaling, AAAS, Washington, DC 20005, USA

Our immune system and the viruses that infect us are in a constant arms race, with one side always trying to outwit the other. One example is the inhibition of the host protein MDA5, a member of the retinoic acid–inducible gene 1 (RIG-I)–like receptor (RLR) family of innate immune sensors, by the V protein expressed by parainfluenza virus 5 (PIV5). To better understand how this inhibition is accomplished, Motz et al. solved the crystal structure of PIV5 V protein bound to the adenosine triphosphatase (ATPase) domain of porcine MDA5. This analysis, together with mutational studies using mouse and human versions of MDA5, revealed that the V protein unfolds the ATPase domain of MDA5 and replaces two β strands of this domain’s structural core. These changes disrupt the ATPase hydrolysis site and prevent the formation of filaments by MDA5, which are important for transmitting downstream signals that activate antiviral immunity. Mutation of just two amino acids in RLR family member RIG-I also rendered this receptor susceptible to V protein–mediated inhibition.

C. Motz, K. M. Schuhmann, A. Kirchhofer, M. Moldt, G. Witte, K.-K. Conzelmann, K.-P. Hopfner, Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling. Science 339, 690–693 (2013). [Abstract] [Full Text]

Citation: K. L. Mueller, Parainfluenza 5 and MDA5. Sci. Signal. 6, ec43 (2013).

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