Suppression of PACT-induced type I interferon production by herpes simplex virus 1 Us11 protein.
Herpes simplex virus 1 (HSV-1) Us11 protein is a double-stranded RNA-binding protein that suppresses type I interferon production through the inhibition of the cytoplasmic RNA sensor RIG-I. Whether additional cellular mediators are involved in this suppression remains to be determined. In this study, we report on the requirement of cellular double-stranded RNA-binding protein PACT for Us11-mediated perturbation of type I interferon production. Us11 associates with PACT tightly to prevent it from binding with and activating RIG-I. The Us11-deficient HSV-1 was indistinguishable from the Us11-proficient virus in the suppression of interferon production when PACT was compromised. More importantly, HSV-1-induced activation of interferon production was abrogated in PACT knockout murine embryonic fibroblasts. Our findings suggest a new mechanism for viral evasion of innate immunity through which a viral double-stranded RNA-binding protein interacts with PACT to circumvent type I interferon production. This mechanism might also be used by other PACT-binding viral interferon-antagonizing proteins such as Ebola virus VP35 and influenza A virus NS1.
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Chun
C
Kew
Pak-Yin
PY
Lui
Chi-Ping
CP
Chan
Xiang
X
Liu
Shannon Wing Ngor
SW
Au
Ian
I
Mohr
Dong-Yan
DY
Jin
Kin-Hang
KH
Kok
D000818:Animals; D015536:Down-Regulation; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C437968:PLAAT4 protein, human; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins; D018168:Receptors, Retinoic Acid; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D016899:Interferon-beta