Journal article

NSP1 of human rotaviruses commonly inhibits NF-kappa B signalling by inducing beta-TrCP degradation

Izabel JM Di Fiore, Jessica A Pane, Gavan Holloway, Barbara S Coulson

JOURNAL OF GENERAL VIROLOGY | MICROBIOLOGY SOC | Published : 2015

Abstract

Rotavirus is a leading cause of severe gastroenteritis in infants worldwide. Rotavirus nonstructural protein 1 (NSP1) is a virulence factor that inhibits innate host immune responses. NSP1 from some rotaviruses targets host interferon response factors (IRFs), leading to inhibition of type I interferon expression. A few rotaviruses encode an NSP1 that inhibits the NF-κB pathway by targeting β-TrCP, a protein required for IκB degradation and NF-κB activation. Available evidence suggests that these NSP1 properties involve proteosomal degradation of target proteins. We show here that NSP1 from several human rotaviruses and porcine rotavirus CRW-8 inhibits the NF-κB pathway, but cannot degrade IR..

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Grants

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

We are most grateful to John Patton for SA11-4F and SA11-5S rotaviruses and NSP1 cDNA, and Malcolm McCrae for OSU rotavirus. IRF7 and I kappa K epsilon expression plasmids and IFNA1-Luc and IFNB-Luc reporter constructs were a kind gift from Fanxiu Zhu. The TRAF6 expression plasmid was generously provided by Luke O'Neill. This work was supported by the National Health and Medical Research Council of Australia, Project Grant 1023786 and Senior Research Fellowship 628319 (to B. S. C.).