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SIDT1 Localizes to Endolysosomes and Mediates Double-Stranded RNA Transport into the Cytoplasm.
Nguyen, Tan A; Smith, Blake R C; Elgass, Kirstin D; Creed, Sarah J; Cheung, Shane; Tate, Michelle D; Belz, Gabrielle T; Wicks, Ian P; Masters, Seth L; Pang, Ken C.
Afiliación
  • Nguyen TA; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
  • Smith BRC; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
  • Elgass KD; Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia.
  • Creed SJ; Monash Micro Imaging, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
  • Cheung S; Monash Micro Imaging, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
  • Tate MD; Monash Micro Imaging, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
  • Belz GT; Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
  • Wicks IP; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria 3168, Australia; and.
  • Masters SL; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
  • Pang KC; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
J Immunol ; 202(12): 3483-3492, 2019 06 15.
Article en En | MEDLINE | ID: mdl-31061008
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 analog poly(IC), and, when overexpressed, enhances endosomal escape of poly(IC) in vitro. To elucidate the role of SIDT1 in vivo, we generated SIDT1-deficient mice. Similar to Sidt2-/- mice, SIDT1-deficient mice produced significantly less type I IFN following infection with HSV type 1. In contrast to Sidt2-/- mice, however, SIDT1-deficient animals showed no impairment in survival postinfection with either HSV type 1 or encephalomyocarditis virus. Consistent with this, we observed that, unlike SIDT2, tissue expression of SIDT1 was relatively restricted, suggesting that, whereas SIDT1 can transport extracellular dsRNA into the cytoplasm following endocytosis in vitro, the transport activity of SIDT2 is likely to be functionally dominant in vivo.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Endosomas / Herpesvirus Humano 1 / Infecciones por Cardiovirus / Citoplasma / Proteínas de Transporte de Nucleótidos / Virus de la Encefalomiocarditis / Herpes Simple / Lisosomas Límite: Animals Idioma: En Revista: J Immunol Año: 2019 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Endosomas / Herpesvirus Humano 1 / Infecciones por Cardiovirus / Citoplasma / Proteínas de Transporte de Nucleótidos / Virus de la Encefalomiocarditis / Herpes Simple / Lisosomas Límite: Animals Idioma: En Revista: J Immunol Año: 2019 Tipo del documento: Article País de afiliación: Australia