NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I.
Retinoic acid-inducible gene I (RIG-I) has recently been identified as one of the key intracellular sensors of virus infection. RIG-I binds to cytosolic double-stranded RNA and initiates a signaling cascade that leads to the activation of transcription factors required for expression of type I interferon (IFN-I). Previous evidence suggests that nonstructural protein 1 (NS1) encoded by influenza A virus (IAV) suppresses IFN-I secretion in virus-infected cells by an unknown mechanism. In the present study, we demonstrate that RIG-I is required for induction of IFN-I in an IAV-infected human lung epithelial cell line. Knockdown of RIG-I expression by RNA interference greatly impairs production of IFN-beta in cells infected with different strains of wild-type IAV. Furthermore, co-expression of IAV NS1 down-regulates production of IFN-beta induced by RIG-I agonists, and ectopic expression of RIG-I inhibits the replication of IAV. These results provide further information on the mechanism by which IAV NS1 antagonizes the host antiviral response.
Guo
Zhu
Z
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Chen
Li-mei
LM
Zeng
Hui
H
Gomez
Jorge A
JA
Plowden
Julie
J
Fujita
Takashi
T
Katz
Jacqueline M
JM
Donis
Ruben O
RO
Sambhara
Suryaprakash
S
D003593:Cytoplasm / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism* / Q000502:physiology; D007251:Influenza, Human; D007370:Interferon Type I / Q000096:biosynthesis; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000821:virology; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D007370:Interferon Type I; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1