Journal article
SIDT1 localizes to endolysosomes and mediates double-stranded RNA transport into the cytoplasm
TA Nguyen, BRC Smith, KD Elgass, SJ Creed, S Cheung, MD Tate, GT Belz, IP Wicks, SL Masters, KC Pang
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2019
Abstract
dsRNA is a common by-product of viral replication and acts as a potent trigger of antiviral immunity. SIDT1 and SIDT2 are closely related members of the SID-1 transmembrane family. SIDT2 functions as a dsRNA transporter and is required to traffic internalized dsRNA from endocytic compartments into the cytosol for innate immune activation, but the role of SIDT1 in dsRNA transport and in the innate immune response to viral infection is unclear. In this study, we show that Sidt1 expression is upregulated in response to dsRNA and type I IFN exposure and that SIDT1 interacts with SIDT2. Moreover, similar to SIDT2, SIDT1 localizes to the endolysosomal compartment, interacts with the long dsRNA ana..
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Awarded by Howard Hughes Medical Institute
Funding Acknowledgements
This work was supported by the Australian National Health and Medical Research Council (NHMRC; Grants 520574 and 1064591), the Royal Australasian College of Physicians, the Menzies Foundation, the Contributing to Australian Scholarship and Science Foundation (Grants SM13-4846 and SM14-5566), the Reid Family Trust, and the Royal Children's Hospital Foundation (all to K.C.P., T.A.N., and B.R.C.S.). T.A.N. was supported by Cancer Council Victoria and the Lung Foundation Australia. M.D.T. was supported by Australian NHMRC Fellowship 1123319. G.T.B. was supported by Australian NHMRC Fellowship 1135898 and Grant 1054925. S.L.M. acknowledges funding from NHMRC Grants 1144282, 1142354, and 1099262, The Sylvia and Charles Viertel Foundation, a Howard Hughes Medical Institute-Wellcome International Research Scholarship, and GlaxoSmithKline. I.P.W. is supported by Australian NHMRC Program Grant 1023407 and Clinical Practitioner Fellowship 0123462.