How viruses interfere with interferon

Double-stranded RNA is a warning flag to the cell, indicating the presence of a virus. In 2004, Takashi Fujita and colleagues at Tokyo Metropolitan Institute of Medical Science identified an RNA-helicase, retinoic acid inducible gene I (RIG-I), as linking dsRNA and the interferon response.1 In the same year, Richard Randall at the University of St. Andrews in Scotland and his group revealed that the V protein of paramyxoviruses short-circuits the interferon response by binding mda-5, a

Sep 1, 2006
Charles Q. Choi

Double-stranded RNA is a warning flag to the cell, indicating the presence of a virus. In 2004, Takashi Fujita and colleagues at Tokyo Metropolitan Institute of Medical Science identified an RNA-helicase, retinoic acid inducible gene I (RIG-I), as linking dsRNA and the interferon response.1 In the same year, Richard Randall at the University of St. Andrews in Scotland and his group revealed that the V protein of paramyxoviruses short-circuits the interferon response by binding mda-5, a similar RNA helicase, not previously linked with interferon production.2

Robert Lamb at Northwestern University in Evanston, Ill., says that as a consequence, "investigations are being conducted on just about every virus as to interactions with mda-5 and RIG-I."

Questions remain. While dsRNA can activate both mda-5 and RIG-I, Randall says it's unclear whether they recognize slightly different forms of dsRNA or other viral structures. "Also, it needs to be established whether or not some form of regulatory crosstalk occurs between mda-5, RIG-I and other cellular signaling cascades," he adds.

References

1. M. Yoneyama et al., "The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses," Nat Immunol, 5:730-7, 2004. (Cited in 207 papers) 2. J. Andrejeva et al., "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-b promoter," Proc Natl Acad Sci, 101:17264-9, 2004. (Cited in 81 papers)