Interferon-inducible protein SCOTIN interferes with HCV replication th…
첨부파일
- 첨부된 파일이 없습니다.
- 담당교수Joo-Yeon Yoo
- 조회3,438
- 작성자최고관리자
- 2017-10-23
관련링크
본문
Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the
autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER)
protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion
production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A)
protein, which is a critical factor for HCV RNA replication, interacts with the IFN-b-inducible
protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore,
the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells
and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall
flow of autophagy; however, it is a substrate for autophagic degradation. The physical
association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and
Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation.
Altogether, our findings suggest that IFN-b-induced SCOTIN recruits the HCV NS5A protein
to autophagosomes for degradation, thereby restricting HCV replication.
DOI: 10.1038/ncomms10631 OPEN
1
autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER)
protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion
production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A)
protein, which is a critical factor for HCV RNA replication, interacts with the IFN-b-inducible
protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore,
the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells
and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall
flow of autophagy; however, it is a substrate for autophagic degradation. The physical
association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and
Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation.
Altogether, our findings suggest that IFN-b-induced SCOTIN recruits the HCV NS5A protein
to autophagosomes for degradation, thereby restricting HCV replication.
DOI: 10.1038/ncomms10631 OPEN
1
