mda-5, but not RIG-I, is a common target for paramyxovirus V proteins.
The induction of IFN-beta by the paramyxovirus PIV5 (formerly known as SV5) is limited by the action of the viral V protein that targets the cellular RNA helicase mda-5. Here we show that 12 other paramyxoviruses also target mda-5 by a direct interaction between the conserved cysteine-rich C-terminus of their V proteins and the helicase domain of mda-5. The inhibition of IFN-beta induction is not species-restricted, being observed in a range of mammalian cells as well as in avian cells, and we show that the inhibition of mda-5 function is also not restricted to mammalian cells. In contrast, the V proteins do not bind to the related RNA helicase RIG-I and do not inhibit its activity. The relative contributions of mda-5 and RIG-I to IFN-beta induction are discussed.
Childs
Kay
K
Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, UK.
Stock
Nicola
N
Ross
Craig
C
Andrejeva
Jelena
J
Hilton
Louise
L
Skinner
Michael
M
Randall
Richard
R
Goodbourn
Stephen
S
D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000096:biosynthesis; D008969:Molecular Sequence Data; D045402:Parainfluenza Virus 5 / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D015678:Viral Structural Proteins / Q000737:chemistry / Q000378:metabolism*
C097019:V protein, Simian parainfluenza virus 5; D015678:Viral Structural Proteins; D016899:Interferon-beta; D053487:DEAD-box RNA Helicases