Merck
  • Galectin-9 restricts hepatitis B virus replication via p62/SQSTM1-mediated selective autophagy of viral core proteins.

Galectin-9 restricts hepatitis B virus replication via p62/SQSTM1-mediated selective autophagy of viral core proteins.

Nature communications (2022-01-29)
Kei Miyakawa, Mayuko Nishi, Michinaga Ogawa, Satoko Matsunaga, Masaya Sugiyama, Hironori Nishitsuji, Hirokazu Kimura, Makoto Ohnishi, Koichi Watashi, Kunitada Shimotohno, Takaji Wakita, Akihide Ryo
摘要

Autophagy has been linked to a wide range of functions, including a degradative process that defends host cells against pathogens. Although the involvement of autophagy in HBV infection has become apparent, it remains unknown whether selective autophagy plays a critical role in HBV restriction. Here, we report that a member of the galectin family, GAL9, directs the autophagic degradation of HBV HBc. BRET screening revealed that GAL9 interacts with HBc in living cells. Ectopic expression of GAL9 induces the formation of HBc-containing cytoplasmic puncta through interaction with another antiviral factor viperin, which co-localized with the autophagosome marker LC3. Mechanistically, GAL9 associates with HBc via viperin at the cytoplasmic puncta and enhanced the auto-ubiquitination of RNF13, resulting in p62 recruitment to form LC3-positive autophagosomes. Notably, both GAL9 and viperin are type I IFN-stimulated genes that act synergistically for the IFN-dependent proteolysis of HBc in HBV-infected hepatocytes. Collectively, these results reveal a previously undescribed antiviral mechanism against HBV in infected cells and a form of crosstalk between the innate immune system and selective autophagy in viral infection.

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Sigma-Aldrich
MG-132, A cell-permeable, potent, reversible proteasome inhibitor (Ki = 4 nM).
Millipore
EZview Red 抗-FLAG® M2 亲和凝胶, clone M2
Millipore
EZview Red 抗-HA 亲和凝胶
Sigma-Aldrich
巴弗洛霉素A1,灰色链霉菌, Bafilomycin A1, CAS 88899-55-2, acts as a highly potent and specific inhibitor of vacuolar-type H+-ATPase (Ki = 500 pM). Blocks the fusion of autophagosome with lysosome.
Millipore
EZview 红色c-Myc亲和凝胶抗体
Sigma-Aldrich
泛素 人, recombinant, expressed in E. coli (N-terminal histidine tagged)
Sigma-Aldrich
泛素激活酶 E1 人, ≥95% (SDS-PAGE)