RGD Reference Report - TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis. - Rat Genome Database

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TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis.

Authors: Aizawa, Sayaka  Okamoto, Toru  Sugiyama, Yukari  Kouwaki, Takahisa  Ito, Ayano  Suzuki, Tatsuya  Ono, Chikako  Fukuhara, Takasuke  Yamamoto, Masahiro  Okochi, Masayasu  Hiraga, Nobuhiko  Imamura, Michio  Chayama, Kazuaki  Suzuki, Ryosuke  Shoji, Ikuo  Moriishi, Kohji  Moriya, Kyoji  Koike, Kazuhiko  Matsuura, Yoshiharu 
Citation: Aizawa S, etal., Nat Commun. 2016 May 4;7:11379. doi: 10.1038/ncomms11379.
RGD ID: 40924634
Pubmed: PMID:27142248   (View Abstract at PubMed)
PMCID: PMC4857398   (View Article at PubMed Central)
DOI: DOI:10.1038/ncomms11379   (Journal Full-text)

Signal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin-proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H13Mousesteatotic liver disease  IMP associated with hepatitisRGD 
HM13Humansteatotic liver disease  ISOH13 (Mus musculus)associated with hepatitisRGD 
Hm13Ratsteatotic liver disease  ISOH13 (Mus musculus)associated with hepatitisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hm13  (histocompatibility minor 13)

Genes (Mus musculus)
H13  (histocompatibility 13)

Genes (Homo sapiens)
HM13  (histocompatibility minor 13)


Additional Information